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  • Gestational Trophoblastic Disease -

    1. 1. Gestational Trophoblastic Disease Ermos Nicolaou Fetal Medicine Centre Chris Hani Baragwanath Hospital University of the Witwatersrand
    2. 2. Gestational Trophoblastic Disease (GTD) is a relatively rare event with a calculated incidence of 1/714 live births. There is evidence of ethnic variation in the incidence of GTD in the UK, with women from Asia having a higher incidence compared with non-Asian women (1/387 versus 1/752 live births). This may under-represent the true incidence of the disease because of problems with reporting, particularly with regard to partial moles.
    3. 3. <ul><li>Hydatiform mole </li></ul><ul><li>Invasive mole </li></ul><ul><li>Choriocarcinoma </li></ul><ul><li>Placental site trophoblastic tumor </li></ul>Partial Complete GESTATIONAL TROPHOBLASTIC DISEASE
    4. 4. Epidemiology <ul><li>The incidence of molar pregnancy varies in different parts of the </li></ul><ul><li>world. </li></ul><ul><li>Women of Asian origin: 1 in 550 to 1 in 600. </li></ul><ul><li>Women of European origin: 1 in 1200 live births </li></ul>
    5. 5. <ul><li>Age is probably the most important factor in the incidence of </li></ul><ul><li>developing complete hydatidiform mole. </li></ul><ul><li>Where the incidence for women aged 25 to 29 is standardized </li></ul><ul><li>as 1, the risk is </li></ul><ul><li>6 X in women who become pregnant under 15 years </li></ul><ul><li>411 X in patients who become pregnant over the age of 50 </li></ul>Epidemiology
    6. 6. North America and Europe: Partial mole 1/700 Complete mole 1/1500-2000 Asian Countries: Partial mole 1/120 Complete mole 1/350-500 HYDATIDIFORM MOLE Incidence
    7. 7. 1. Maternal age > 40 years < 15 years 2. Paternal age > 45 years 3. Previous hydatidiform mole 1 st 1-2% 2 nd 15-28% 4. Vitamin A deficiency HYDATIDIFORM MOLE Risk factors
    8. 8. <ul><li>Background </li></ul><ul><li>Hydatidiform mole is subdivided into complete and partial mole </li></ul><ul><li>based on genetic and histo-pathological features. </li></ul><ul><li>Complete moles are </li></ul><ul><li>diploid </li></ul><ul><li>andro-genetic in origin </li></ul><ul><li>no evidence of fetal tissue. </li></ul><ul><li>Arise as a consequence of </li></ul><ul><li>duplication of the haploid sperm following fertilisation of an ‘empty’ ovum ( diandry) </li></ul><ul><li>Some complete moles arise after dispermic fertilisation of an </li></ul><ul><li>“ empty’ ovum. (dispermy) </li></ul>Molar Pregnancy Complete Mole
    9. 9. Empty ovum Empty ovum 46XX 46XX or 46XY 23X or Y 23X 23X Complete Mole (46XX diploid) Complete Mole (46XX or 46XY, diploid) A single sperm fertilizes an empty ovum, with duplication of the 23X haploid set of chromosomes, giving rise to a homozygous diploid complete mole. Two sperms with two independent haploid sets of chromosomes fertilize an empty ovum, producing a dyspermic complete mole with either 46XX or 46XY karyotype. COMPLETE MOLE Modified from Cheung, 1995
    10. 10. Complete molar pregnancy <ul><li>Complete hydatidiform mole forms a multivesicular mass with </li></ul><ul><li>diffuse hydropic villi and a variable degree of trophoblastic </li></ul><ul><li>proliferation. </li></ul><ul><li>There is usually no evidence of a foetus . This conceptus is diploid </li></ul><ul><li>and androgenetic in origin. </li></ul><ul><li>The incidence of a GT Tumour is approximately 1000X more likely </li></ul><ul><li>following a complete hydatidiform mole than after a full-term </li></ul><ul><li>pregnancy. </li></ul><ul><li>One possible explanation is that genomic imprinting plays a </li></ul><ul><li>role in tumourigenesis since the complete mole is androgenetic in </li></ul><ul><li>origin. </li></ul>
    11. 11. Father F
    12. 17. <ul><li>Triploid in origin with usually two sets of paternal haploid genes and </li></ul><ul><li>one set of maternal haploid genes. </li></ul><ul><li>They occur, in almost all cases, following dispermic fertilisation of an ovum. There is usually evidence of a fetus or fetal red blood cells. </li></ul><ul><li>In some cases failure of meiosis I or II in the ovum leads to Triploidy with 46 maternally derived chromosomes and 23 paternal </li></ul>Partial Molar Pregnancy
    13. 18. 23X 23X Dyspermy 23X/23Y or 23X/23X 23Y Partial Mole (69XXY, or 69XXX, or 69XYY triploid) PARTIAL MOLE 23X 23X 23Y 69XXY Fertilization of a normal 23X haploid ovum by two sperms, producing a triploid partial mole with either 69XXY, 69XXX or 69XYY karyotype Modified from Cheung, 1995
    14. 19. Triploidy <ul><li>mild ventriculomegaly, </li></ul><ul><li>micrognathia, </li></ul><ul><li>cardiac abnormalities, </li></ul><ul><li>myelomeningocoele, </li></ul><ul><li>syndactyly, </li></ul><ul><li>‘ hitch-hiker’ toe deformity. </li></ul>When extra set of chromosomes is paternally derived , is associated with a molar placenta and the pregnancy rarely persists beyond 20 weeks. When there is a double maternal chromosome contribution, the pregnancy may persist into the third trimester. The placenta may be of normal consistency and the fetus demonstrates severe asymmetrical growth retardation
    15. 20. Fetal or embryonic tissue absent present Hydatiform swelling of chorionic villi extensive focal Trophoblastic hyperplasia extensive focal Scalloping of chorionic villi absent present Trophoblastic stromal inclusions absent present Karyotype 46XX (90%); Triploid (69 XXY) 46XY (10%) Complete mole Partial mole Cohn DE, Herzog TJ. Curr Opin Oncol 2000 Sep; 12(5):492-6 FEATURES OF PARTIAL AND COMPLETE MOLE
    16. 23. Persistent GTD <ul><li>The term persistent &quot;gestational trophoblastic disease&quot; is widely </li></ul><ul><li>used to describe the situation where a woman has had a </li></ul><ul><li>hydatidiform mole and still has persistently raised human chorionic </li></ul><ul><li>gonadotrophin (hCG) estimations </li></ul><ul><li>Since in the majority of cases the disease either remits </li></ul><ul><li>spontaneously or can be successfully treated without further </li></ul><ul><li>pathological sampling, it is difficult to say exactly in what </li></ul><ul><li>proportion of patients their hydatiform mole modulates to </li></ul><ul><li>choriocarcinoma. </li></ul><ul><li>This event probably happens in 3% to 5% of patients who have had </li></ul><ul><li>a complete hydatidiform mole </li></ul>
    17. 24. Gestational Trophoblastic Disease <ul><li>Persistent GTD may develop </li></ul><ul><li>After a molar pregnancy, </li></ul><ul><li>After a non-molar pregnancy </li></ul><ul><li>After a live birth (~ 1/50 000) </li></ul>
    18. 25. Gestational Trophoblastic Tumours <ul><li>Overview </li></ul><ul><li>GTT are unique in cancer biology in that they follow </li></ul><ul><li>either a normal or abnormal pregnancy, </li></ul><ul><li>the tumours contain paternal genes and are therefore an </li></ul><ul><li>allograft in the maternal host. </li></ul>
    19. 26. Distribution of Immunocompetent Cells in Decidua of Controlled and Uncontrolled(Choriocarcinoma/Hydatidiform mole)Trophoblast Invasion S. Knoeller, E. Lim, L. Aleta, et al AJRI 2003; 50 : 41–47 <ul><li>A significantly increased number of T lymphocytes positive for </li></ul><ul><li>CD8, CD3 are observed in Chorio-Carcinoma and Hydatiform Mole </li></ul><ul><li>compared with samples from Normal Pregnancies (P < 0.001). </li></ul><ul><li>T cells are known to be prominent only during early pregnancy and </li></ul><ul><li>are rapidly down regulated in normal human pregnancies. </li></ul><ul><li>It seems to be likely that T cells are important for implantation to occur with respect to controlling natural killer (NK) cell activity </li></ul>
    20. 27. <ul><li>Lymphocytes positive for natural killer (NK) cell marker CD56 are </li></ul><ul><li>significantly decreased in CC and HM versus NP (P < 0.001). </li></ul><ul><li>In normal decidua the number of CD56 NK cells is very prominent </li></ul><ul><li>and increases with gestational age. </li></ul><ul><li>Natural killer cells discriminate self from non-self in a manner </li></ul><ul><li>distinct from T cells. </li></ul><ul><li>NK cells exhibit cytotoxicity against missing-self by killing all cells </li></ul><ul><li>but so-called self cells. </li></ul>
    21. 28. <ul><li>Trophoblast cells appear to evade the attack by the NK cells via </li></ul><ul><li>interactions with “killer inhibitory receptor molecules” on CD56+ve </li></ul><ul><li>Lymphocytes </li></ul>Choriocarcinoma Hydatidiform Mole Normal Pregnancy
    22. 29. A–C depicts staining against cytokeratin-positive cells,which identify trophoblast / tumor cells, marked by brown staining. D–F shows representative examples of the distribution and density of CD8+ cells, which are present as clusters in CC (D) and HM (E). S. Knoeller, E. Lim, L. Aleta, et al AJRI 2003; 50: 41–47 Choriocarcinoma Hydatidiform Mole Normal Pregnancy
    23. 30. Study Conclusion <ul><li>Invasion is not only a question of reproductive immunology but also a question of tumor immunology </li></ul>
    24. 31. Invasive Hydatidiform Mole <ul><li>Invasive hydatidiform mole (complete or partial) is common since </li></ul><ul><li>molar trophoblast invades the myometrium in most cases. </li></ul><ul><li>Pathologically invasive hydatidiform mole can be diagnosed only </li></ul><ul><li>when sufficient myometrium is made available to the pathologist </li></ul><ul><li>either on curettings or by hysterectomy </li></ul>
    25. 32. Invasive Hydatidiform Mole <ul><li>An invasive mole retains hydropic villi, which penetrate the uterine wall. </li></ul><ul><li>Can cause uterine rupture and can be life threatening. </li></ul><ul><li>Hydropic villi may embolize to distant organs, but this tumor does not have metastatic potential. </li></ul><ul><li>Cure is possible by hysterectomy or chemotherapy. </li></ul>
    26. 33. Choriocarcinoma <ul><li>It is an unusual tumour in that it stimulates virtually no stromal </li></ul><ul><li>reaction and is therefore essentially a mixture of haemorrhage and </li></ul><ul><li>necrosis with tumour cells scattered within the mass. </li></ul><ul><li>Tumour cells can be scanty and present problems of pathological </li></ul><ul><li>interpretation if the possibility of choriocarcinoma has not been </li></ul><ul><li>raised. </li></ul><ul><li>The pathology of choriocarcinoma is reflected in its clinical </li></ul><ul><li>behaviour with widespread intravascular dissemination to lungs, </li></ul><ul><li>brain and other sites. </li></ul>
    27. 34. Choriocarcinoma <ul><li>Is a very aggressive malignant tumor and arises either from </li></ul><ul><li>gestational chorionic epithelium or less frequently, from </li></ul><ul><li>totipotential cells within gonads or elsewhere. </li></ul><ul><li>Incidence is 1/ 30,000 pregnancies in US. </li></ul><ul><li>More common in Asian and African countries. </li></ul>
    28. 35. Choriocarcinoma <ul><li>Most cases are discovered by the appearance of a bloody, brownish </li></ul><ul><li>discharge, accompanied by a rising titer of HCG, particularly the </li></ul><ul><li>beta subunit. </li></ul><ul><li>Usually appear as very hemorrhagic, necrotic masses within the </li></ul><ul><li>uterus. </li></ul><ul><li>Widespread dissemination via blood, lung (50%), vagina (30-40%), </li></ul><ul><li>brain, liver and kidney. </li></ul>
    29. 36. Placental site trophoblastic tumours <ul><li>Placental site trophoblastic tumours are now recognised as a </li></ul><ul><li>separate entity. </li></ul><ul><li>rare and </li></ul><ul><li>are composed mainly of cytotrophoblastic cells </li></ul><ul><li>tend to be locally invasive </li></ul><ul><li>less widely metastatic than choriocarcinoma </li></ul><ul><li>The optimal management of patients with placental site </li></ul><ul><li>trophoblastic tumours is unclear. </li></ul><ul><li>This is because </li></ul><ul><li>the tumours are rare and </li></ul><ul><li>their biological behaviour does appear to be variable. </li></ul>
    30. 37. <ul><li>Where the disease is localised to the uterus, hysterectomy is the </li></ul><ul><li>treatment of choice . </li></ul><ul><li>A small number of patients treated with intensive chemotherapy </li></ul><ul><li>initially have achieved complete remission but the chemosensitivity </li></ul><ul><li>of placental site trophoblastic tumours appears to be quite variable </li></ul>Placental site trophoblastic tumours
    31. 38. Clinical presentation <ul><li>The most common presentation of a patient with a GTD is </li></ul><ul><li>vaginal bleeding towards the end of the first trimester of pregnancy. </li></ul><ul><li>nausea and vomiting and </li></ul><ul><li>uterus larger for dates than for a normal pregnancy. </li></ul><ul><li>Since the quantity of hCG produced by a normal pregnancy can vary </li></ul><ul><li>over quite a wide range, the initial hCG estimation is not helpful in </li></ul><ul><li>differentiating between a pregnancy and a hydatidiform mole. </li></ul>
    32. 39. COMPLETE HYDATIFORM MOLE CLINICAL FEATURES Vaginal bleeding (anemia) 97% Excessive uterine size 50% Theco-lutein ovarian cysts 50% Preeclampsia 27% Hyperemesis 25% Hyperthyroidism 7% Trophoblastic embolization 2% (respiratory distress)
    33. 40. The increasing performance of ultrasound examination, either routinely in the first trimester or for management of early pregnancy complications, allows evacuation of most pregnancies affected by hydatiform mole prior to development of the classic sonographic and pathological features. ULTRASOUND FINDINGS
    34. 41. Multiple hypoechoic areas extensive focal Increased echogenicity extensive focal Enlarged uterine volume present absent Theca-lutein cysts present absent > Ø gestational sac - present < Uterine artery PI present - Complete mole Partial mole ULTRASOUND FINDINGS
    35. 42. COMPLETE MOLE “ snow storm”
    36. 43. PARTIAL MOLE “ Swiss cheese”
    37. 44. Diagnosis of Gestational Trophoblastic Disease <ul><li>Increasing use of ultrasound in early pregnancy has led to the </li></ul><ul><li>earlier diagnosis of molar pregnancy. </li></ul><ul><li>The majority of histologically proven complete moles however are </li></ul><ul><li>associated with an ultrasound diagnosis of delayed miscarriage or </li></ul><ul><li>anembryonic pregnancy </li></ul><ul><li>The ultrasound features of a complete mole are reliable but the </li></ul><ul><li>ultrasound diagnosis of a partial molar pregnancy is more complex. </li></ul><ul><li>RCOG, February 2004 </li></ul>
    38. 45. ‘ T he diagnostic implications of routine ultrasound examination in histologically confirmed early molar pregnancies ‘ OBJECTIVE : to determine the sonographic findings of routine ultrasound examinations in patients with a proven histological diagnosis of complete or partial hydati f orm mole. Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662
    39. 46. Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662 <ul><li>retrospective review ( 6-month period ) </li></ul><ul><li>194 cases referred to the National Trophoblastic Disease Surveillance Centre (Charing Cross Hospital) with suspected molar pregnancies </li></ul><ul><li>review of ultrasound findings </li></ul><ul><li>fin al histological diagnosis </li></ul>
    40. 47. 194 63 (33%) hydatiform mole 155 131 (67%) missed misc./anembryonic pregn. Ultrasonographic diagnosis Histological diagnosis 53 (84%) hydatiform mole 64 compl mole 91 partial mole 37 (58%) mole 16 (17%) mole Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662
    41. 48. <ul><li>The majority of cases of molar pregnancy present sonographically as missed abortion/anembryonic pregnancy ( importance of histological examination ). </li></ul><ul><li>A false-positive result on U.S. is relatively unlikely . </li></ul><ul><li>It is highly likely that cent re s with specific expertise can identify some cases more accurately . </li></ul>Sebire NJ et al . Ultra sound Obste t Gynecol 2001 Dec; 18 ( 6 ): 662 CONCLUSION of study
    42. 49. DIAGNOSTIC ACCURACY OF ULTRASONOGRAPHY IN COMPLETE MOLAR PREGNANCY Sebire et al. (2000) 58% Lazarus et al. (1999) 57% Benson et al. (2000) 79% Lindholm et al. (1999) 80%
    43. 50. <ul><li>Presence of multiple soft markers including, </li></ul><ul><li>cystic spaces in the placenta and </li></ul><ul><li>a ratio of transverse to AP dimension of the gestation sac </li></ul><ul><li>of > 1.5 </li></ul><ul><li>When there is diagnostic doubt about the possibility of a combined </li></ul><ul><li>molar pregnancy with a viable fetus then ultrasound examination </li></ul><ul><li>should be repeated before intervention. </li></ul>Diagnosis of Gestational Trophoblastic Disease
    44. 51. DIFFERENTIAL DIAGNOSIS partial mole hydatiform mole + viable fetus mesenchymal dysplasia Fetus absent complete mole Fetus present
    45. 52. PARTIAL MOLE More than 90% of partial moles are found in triploid fetuses. Feto-placental ultrasound findings n % Fetal anatomic defects 65 92.9 1 10 14.3 2 23 32.9 >2 32 45.7 Asymmetrical growth restriction 45 64.2 Placental molar changes 20 28.6 Amniotic fluid changes 33 47.1 Olygohydramnios 31 44.2 Polyhydramnios 2 2.9 Jauniaux E, Nicolaides KH: Placenta 1997, 18; 701-6
    46. 53. Ultrasound abnormalities in triploid fetuses Malformed hands 34 52.3 Ventriculomegaly 24 36.9 Heart abnormalities 22 33.9 Micrognathia 17 26.2 Hyperechogenic bowel 10 15.4 Renal malformations 8 12.3 Increased nuchal thickness 8 12.3 Spina bifida 5 7.7 Talipes equinovarous 5 7.7 Dandy-Walker malformation 5 7.7 Collapsed stomach 5 7.7 Single umbilical artery 4 6.2 Omphalocele 4 6.2 Holoprosencephaly 2 3.1 Hydrops 2 3.1 Bilateral pleural effusion 2 3.1 Ascites 2 3.1 Diaphragmatic hernia 1 1.5 Kyphoscoliosis 1 1.5 Cleft lip and palate 1 1.5 Variables n = 65 % Jauniaux E, Nicolaides KH: Placenta 1997, 18; 701-6
    47. 54. PARTIAL MOLE FIRST TRIMESTER DIAGNOSIS <ul><li>Discrepancy between CRL and LMP </li></ul><ul><li>Increased fetal nuchal translucency </li></ul><ul><li>Increased ß HCG levels for gestational age </li></ul>
    48. 55. GTD and Twin Pregnancy
    49. 56. Incidence 1:22.000 – 1:100.000 Variants viable fetus with partial hydatiform mole viable fetus with complete hydatiform mole GTD and Twin Pregnancy
    50. 57. GTD and Twin Pregnancy <ul><li>If there is one viable fetus and the other pregnancy is molar, the </li></ul><ul><li>pregnancy could be allowed to proceed if the mother wishes, </li></ul><ul><li>following appropriate counselling. </li></ul><ul><li>The probability of achieving a viable baby is 40% and there is a risk </li></ul><ul><li>of complications such as pulmonary embolism and pre-eclampsia. </li></ul><ul><li>There is no increased risk of developing persistent GTN after such </li></ul><ul><li>a twin pregnancy and outcome after chemotherapy is unaffected. </li></ul>
    51. 58. Prognosis Miscarriage 50% Stillbirth <32 wks 30% Preterm delivery <32 wks 30% Pre-eclampsia > 50% COMPLETE HYDATIFORM MOLE AND COEXISTING VIABLE FETUS
    52. 59. Management of GTD <ul><li>Suction curettage is the method of choice of evacuation for </li></ul><ul><li>complete molar pregnancies. </li></ul><ul><li>Because of the lack of fetal parts a suction catheter, up to a </li></ul><ul><li>maximum of 12 mm, is usually sufficient to evacuate all complete </li></ul><ul><li>molar pregnancies </li></ul><ul><li>Medical termination of complete molar pregnancies, including </li></ul><ul><li>cervical preparation prior to suction evacuation, should be avoided </li></ul><ul><li>where possible because of the potential to embolise and </li></ul><ul><li>disseminate trophoblastic tissue through the venous system </li></ul>
    53. 60. <ul><li>In partial molar pregnancies where the size of the fetal parts </li></ul><ul><li>deters the use of suction curettage, medical termination can be </li></ul><ul><li>used. </li></ul><ul><li>These women may be at an increased risk of requiring treatment </li></ul><ul><li>for persistent trophoblastic neoplasia, although the proportion of </li></ul><ul><li>women with partial molar pregnancies needing chemotherapy is low </li></ul><ul><li>(0.5%) </li></ul>Management of GTD
    54. 61. Histological examination of products of conception <ul><li>All products of conception obtained after evacuation </li></ul><ul><li>(medical or surgical) should undergo histological examination </li></ul><ul><li>in order to exclude trophoblastic neoplasia. </li></ul><ul><li>Ploidy status may help in distinguishing partial from complete </li></ul><ul><li>moles. </li></ul>
    55. 62. Persistent GTD after a non-molar pregnancy <ul><li>Persistent GTD can occur after non-molar pregnancies. </li></ul><ul><li>Presenting symptoms: </li></ul><ul><li>Vaginal bleeding is common </li></ul><ul><li>Symptoms from metastatic disease, such as dyspnoea or abnormal </li></ul><ul><li>neurology </li></ul><ul><li>The prognosis for women with GTD after non-molar pregnancies </li></ul><ul><li>may be worse </li></ul><ul><li>-21% mortality after a live birth, </li></ul><ul><li>- 6% after a non-molar miscarriage </li></ul><ul><li>Reason: ? due to the delay in diagnosis (0.5–58.0 months) </li></ul>
    56. 63. Gestational Tropholastic Neoplasia- Requirement for diagnosis <ul><li>4 or more values of hCG plateau over ay least 3 weeks </li></ul><ul><li>A rise of hCG of 10% or greater for > 3 values over at least 2 weeks </li></ul><ul><li>Presence of Choriocarcinoma </li></ul><ul><li>Persistence of hCG 6 months after mole evacuation </li></ul>
    57. 64. Treatment of persistent GTD <ul><li>Women with persistent GTD should be treated at a specialist </li></ul><ul><li>centre with appropriate chemotherapy. </li></ul><ul><li>Need for chemotherapy following a complete mole is 15% </li></ul><ul><li>following a partial mole 0.5 % </li></ul><ul><li>Disease risk is scored according to the FIGO staging for GTN </li></ul>
    58. 65. FIGO Staging <ul><li>STAGE </li></ul><ul><li>Confined to the uterus </li></ul><ul><li>Outside of uterus, limited to genital structures </li></ul><ul><li>Extends to lungs +- genital tract involvement </li></ul><ul><li>All other metastatic sites </li></ul>
    59. 67. FIGO score Low Score <6 High Score > 7 >100.000 >10.000-100.000 1.000- 10.000 <1.000 Pretreat. hCG 12 7-12 4-6 <4 Interval (months) Term pregnancy abortion Hydat Mole Antecedent pregnancy 4 2 1 >39 0 <39 Age Combined Single drug Previous failed chemo >8 4-8 1-4 0 No of metastasis Brain, Liver GI tract Spleen, kidney Site of metastasis 5cm 3-4cm Largest tumour size
    60. 68. <ul><li>Women scoring <6 (low risk) </li></ul><ul><li>Methotrexate imi on alternate days, each course consisting of </li></ul><ul><li>four injections </li></ul><ul><li>followed by six rest days </li></ul><ul><li>Women who develop resistance to Methotrexate are treated with a </li></ul><ul><li>combination of intravenous Actinomycin D and Etoposide. </li></ul>Treatment of persistent GTD
    61. 69. <ul><li>Women scoring >7 (high risk) receive combination chemotherapy. </li></ul><ul><li>IV Etoposide, Methotrexate, Actinomycin D for 2 days </li></ul><ul><li>followed by Cyclophosphamide and Vincristine (Oncovin) (EMA-CO) </li></ul><ul><li>one week later. </li></ul><ul><li>The course is then repeated after six days. </li></ul><ul><li>Charing Cross Hospital, London </li></ul>Treatment of persistent GTD
    62. 70. Future pregnancy <ul><li>Women should be advised not to conceive until their hCG levels </li></ul><ul><li>have been normal for six months. </li></ul><ul><li>Women who undergo chemotherapy are advised not to conceive for </li></ul><ul><li>one year after completion of treatment </li></ul><ul><li>Risk of a further molar pregnancy is low (~ 2%) </li></ul><ul><li>>98% of women who become pregnant following a molar pregnancy </li></ul><ul><li>will not have a further mole or be at increased risk of obstetric </li></ul><ul><li>complications. </li></ul><ul><li>If a further molar pregnancy does occur, in 68–80% of cases it will </li></ul><ul><li>be of the same histological type </li></ul>
    63. 71. Follow-up and Fertility after Chemotherapy <ul><li>Approximately 90% of patients who want to become pregnant </li></ul><ul><li>following chemotherapy have succeeded and there is no evidence of </li></ul><ul><li>increase in foetal abnormalities. </li></ul><ul><li>Occasionally a G.T.T. can occur or recur after a subsequent normal </li></ul><ul><li>pregnancy </li></ul><ul><li>This emphasises the importance of reconfirming that hCG levels </li></ul><ul><li>return to normal after any subsequent pregnancy in a woman who </li></ul><ul><li>has had a trophoblastic disease event </li></ul>
    64. 72. Contraception and hormone replacement therapy <ul><li>The COC-pill, if taken while hCG levels are raised, may increase the </li></ul><ul><li>need for treatment. </li></ul><ul><li>However, it can be used safely after the hCG levels have returned </li></ul><ul><li>to normal. </li></ul><ul><li>Other forms of hormonal contraception do not appear to be linked </li></ul><ul><li>to an increased need for treatment. </li></ul><ul><li>The small potential risk of using emergency hormonal </li></ul><ul><li>contraception, in women with raised hCG levels, is outweighed by </li></ul><ul><li>the potential risk of pregnancy to the woman. </li></ul><ul><li>Hormone replacement therapy may be used safely once hCG levels </li></ul><ul><li>have returned to normal. </li></ul>
    65. 73. Survival <ul><li>The overall survival in the Charing Cross series, with a maximum </li></ul><ul><li>follow-up of 15 years is ~ 94% </li></ul>
    66. 74. <ul><li>The successful outcome in patients with GTT depends on several factors:- </li></ul><ul><li>(i) Need for a national registration scheme of patients at risk of developing a GTT (ii) The ability to monitor the disease and its response to treatment with serial hCG estimations. (iii) The intrinsic biological property of GTT in being inherently very sensitive to a range of chemotherapeutic agents. </li></ul>Survival
    67. 75. <ul><li>Thank you </li></ul>