By Dr. Nadia Saddam AL.Assady C.A.B.O.G

1. Gestational trophoblastic disorders By Dr. Nadia Saddam AL.Assady C.A.B.O.G

2. It is covers a spectrum of disease caused by trophoblastic proliferative abnormalities. This include: • hydatidiform mole • choriocarcinoma , • invasive mole , • placental site trophoblastic tumor. • Incidence :[ 0.5- 2.5] per l000 pregnancies. • Backgrounds : [50% of cases fallow HM ,25 % a normal pregnancy ,and 25 % miscarriage or ectopic pregnancy.

3. hydatidiform mole: • can be subdivided into complete HM and partial HM based on genetic and histological features. • Complet HM : • Pathogenesis: either empty oocyte fertilized by a normal haploid sperm[23 X] which duplicate itself to complete [46 XX] after meiosis and this occur in[ 96 %]or less commonly an empty oocyte is fertilized by dispermic process [23 Y or23 X] so leading to [46 XX or 46 XY] and this occur in [4 %]of cases.

4. Karyotype : [46 XX or 46 XY] pure paternal contribution [ phenomena of androgenesis]. • Macroscopic features : bunch of small clear grapes and no fetus. • Microscopic features : diffuse hydropic swelling, diffuse trophoblastic hyperplasia, absence of blood vessels and no fetal tissues.

5. Partial HM : • Pathogenesis : either fertilization of normal oocyte by two sperms or fertilization of normal oocyte by single sperm failed to undergo meiosis and carries paternal load of XY result in triploidy 69 chromosomes with double paternal contribution. • Karyotype :[ 69 xxy ]in[ 70 %] ]and[ 69 xyy ]or[ 69 xxx] in [ 27 % ] or double maternal contribution in[ 69 xxx ][ 3 %].

6. Macroscopic features : there is fetal and placental tissues in the fetus there is IUGR ,gross anomalies like hydrocephaly. • Microscopic features : focal hydropic swelling, focal trophoblastic hyperplasia, presence of some blood vessels and fetal tissues with gross anomalies.

7. Epidemiology : • i- ethnicity: more common in Asian than western women like Japan and Korea. • ii-maternal age: women older than 45 years had increase risk and women younger than l5 years had increase risk but less than for older one so extremity of age is a risk factors. • iii- diet and socioeconomic factors: diet low in carotene and vitamin A and low animal fat had high risk also related to protein, folic acid and iron deficiency.

8. iv-blood groups: maternal blood groups B, AB are risk factors group A are protective. • v-previous molar pregnancy: there is increase risk of recurrence and the overall incidence is [0.5 – 2 %] • vi-genetic factors : occur in certain family cluster and in case of repetitive mole.

9. Clinical feature : • It is present as exaggerated S/S of pregnancy depend on the proliferative activity of molar tissues. • a-vaginal bleeding : [ 90 %] which is irregular first trimester bleeding • b-uterus large for date : [ 25 %] because the uterus filled with molar tissues. c-pain from the large theca lutein cysts[ 20 %]resulting from ovarian hyper stimulation by high HCG levels.

10. d- exaggerated S/S of pregnancy : • i-anemia • ii- hyperemsisgravidarum [ 10 %] • iii-hyperthyroidism [ 5 %] • iv-early preeclampsia[ 5 %] • e-embolization : the molar tissues may escapes the uterus through venous outflow and emboli may reach the pulmonary vessels leading to fetal pulmonary embolism. • f-DIC : molar tissues may release thromboplastin to circulation and stimulate fibrin and platelet deposition leading to DIC.

11. Diagnosis : • i-U/S : shows the characteristic "snow storm appearance" and large theca lutein cysts in complete HM and in partial HM fetus may be viable with signs of growth restriction and structural abnormalties. • ii-Quantitative measurement of serum HCG no longer used unless the U/S is unequivocal.

12. Treatment of HM: • The aim of treatment is to eliminate all molar tissues from maternal system without undue delay. • Preparatory steps prior to molar evacuation: • a-preparation of blood because there is risk of bleeding. • b-CBP, coagulation screen and electrolyte check, correct anemia DIC and electrolyte imbalance.

13. c-correct dehydration which may result from hyperemsis. • d-chest x-ray should be done at the time of evacuation of uterus to exclude lung metastasis. • e-treatment of pre eclampsia. • The treatment of HM includes two phases: • Immediate phase : evacuation of mole. • Follow up phase : detection of malignant changes.

14. Immediate phase : • Immediate methods of evacuation of mole : • i-suction curettage: vacuum aspiration using _ve pressure between [_6o to 70 cm Hg] it is the safest and preferable methods and can be used even the uterus larger than [ 20 weeks] this is usually under taken under GA to allow easy cervical dilatation oxytocin drip should be avoided during evacuation of mole because there is theoretical risk of molar tissues dissemination leading to metastasis to lung and brain, but it used may be important to reduce the risk of bleeding so can be used after complete evacuation of mole. The bulk of evacuated mole sent for histopathological examination .

15. ii-uterine stimulation by oxytocin and prostaglandin are poor alternative to suction curettage because • i.voxytocin as primary methods of evacuation of mole is unsatisfactory, because myomaterial response is poor and need long hours of stimulation during which metastasis may takes place. • PGE more effective to stimulate uterine contraction and is safe especially in presence of coexistence fetus in partial mole.

16. iii-hysterectomy : it is indicated in women aged [> 40 years],complete her family and desire sterilization, here hysterectomy may be preferred because in such age groups around [40%] will developed malignant changes later on. • So hysterectomy is usually associated with lesser no, of subsequent chemotherapeutic courses , emergency hysterectomy may be indicated in certain circumstances for controlling massive life threatening hemorrhage • Removal of the ovaries depends on patients age if [ >50 years] so removed if less than that so retain even in presence of theca lutein cyst.

17. Complications of HM: • A-immediate complications • i-massive hemorrhage . • ii-sepsis so antibiotics cover required • iii-preeclampsia may be severe enough to developed fit • B-remote complications includes metastasis and malignant changes • a-[ 80%]of HM under goes spontaneous resolution after curettage • b-[ 15%] develop local invasive mole. • c-[5% develop metastatic choriocarcinoma. • d-[5%] of partial mole develop local invasive mole

18. follow up phase: • this is indicated for[2 years] after evacuation of mole to identify [20% - 25%] who will develop malignant changes or metastasis the rationale of follow up is to ensure that those who require chemotherapy should receive it when it is effective and not given to those who do not need it. • +Second curettage: may be needed if bleeding persist [2 weeks] following 1st evacuation because of incomplete uterine emptying but is not routinely recommended.

19. +contraception for[ 1- 2 years ]: prevent pregnancy for at least [ 1years ] because it result in HCG which cannot be differentiated from that produced by persistent or recurrent gestational trophoblastic tumor • The different types of contraception have different affect on molar tissues • IUCD not advisable because it increase bleeding and may perforate uterus

20. COCP alter behavior of trophoblast cells and prolong their biological life and makes them die slowly, but this is not the case with low dose pills [<30 ugm] oestradiol • Mini pills causes break through bleeding which confuse the clinical picture so the best contraceptive methods is the barrier methods or low estrogen pills until normalization of HCG.

21. +serial HCG levels: this essential in follow up to identify malignant potential groups. Routine assessment of HCG assay started[3 weeks] after evacuation. • Then repeat at [ 2 week] interval and should normalize in [4-6week] after evacuation. After reaching normal level repeat at[ monthly ] interval for the first year and [3 monthly ] interval for the second year. Continue surveillance for [ 2 years ] in complete mole and [6 months] in partial mole. +chest X-ray: Recommended at time of evacuation of uterus repeat monthly until normalization of HCG then repeat at [6, 8,12 months] but if initial CXR normal and HCG decrease no need to repeat it.

22. Indication for chemotherapy : • The task of follow up is to identify the need for chemotherapy which are: • a-first post evacuation HCG level [>20.000 i.u /l in blood ]& [30.000 i.u /l in urine ]. • b-Abnormal HCG curve : • +failure to normalize within [ 6- 8 week] after evacuation. • +increase HCG level at any time. • +plateau of HCG for [ 3 week].

23. c-Evidence of GIT , hepatic or intracranial metastasis. • d-Pulmonary metastasis with increase HCG. • e-Persistent hemorrhage with increase HCG. • f-Any detectable level of HCG [5-6 months after evacuation . • If any indication of chemotherapy detected, patient should be referred to specialized center for consideration of chemo therapy and choosing appropriate protocol according to certain criteria • If none of indications detected in two years period follow up reassure patient and encourage pregnancy.

34. Thank you