1. Case Presentation: Partial molar Pregnancy Dr Haseena Hamdani Avicenna Medical Centre

2. Introduction  Case Report of Partial molar pregnancy.  Brief discussion about partial molar pregnancy.  Role of Diagnostics in Management.

3. Case Report  Asian woman  27years old  Nulliparous  Consanguineous marriage  Combined oral pills for puberty menorrhagia

4. First visit  Presenting Symptoms  Amenorrhoea 6 weeks  Clinical Examination  Urine pregnancy test – positive  PV examination – Bulky soft uterus

5. Follow up visit after 4 weeks  Presenting Symptoms  Amenorrhea 10 weeks  Abdominal USG-  Gestational sac present.  Ill defined fetal echo present.  Cardiac pulsation not seen.  Few small cisterns in part of placenta

6. Second follow up visit after three days  Serum Beta HCG levels-  125,000mIU/ ml,  138,000mIU/ml after 48 hrs.  Repeat USG  Same findings

7. Second follow up visit Clinical impression  ? Partial mole Plan  suction evacuation followed by histological analysis.  Follow up by serum HCG estimation.

8. Treatment  Suction Evacuation done.  Curetted material sent for Histo-pathology.

9. Histo-pathology report  Findings  Fetal tissue with fetal vessels present.  Hydropic degeneration of chorionic villi  Trophoblastic hyperplasia seen at few places. Conclusion  ? Missed abortion with hydropic degeneration of placenta  ? Partial mole ( Correlate clinically). Advice –serum HCG level after 4 weeks

10. Post-evacuation follow up  Irregular scanty bleeding P/V for 3weeks  HCG levels  After 4 weeks-543mIU/ml  After 6 weeks- 58.73mIU/ml  After 8 weeks- 11.67mIU/ml  After 10 weeks- 3.16mIU/ml

11. Post-evacuation follow up  Advice  use combined oral pills for next 6 months,  follow up for HCG levels every month for 6 months.

12. Brief Discussion Gestational trophoblastic Diseases.  Molar pregnancy  Complete molar pregnancy  Partial molar Pregnancy  Invasive Mole  Chorio-carcinoma  Placental-site trophoblastic tumor

13. Characteristics of GTD  Arise from fetal chorion  Secrete HCG  Good response to chemotherapy  Variable Malignant Potential

14. Gestational Trophoblastic Diseases Incidence  Asians 1 in 200- 300  Africans 1 in 800  Caucasians 1 in 2000  Maximum in Indonesia, Japan, and Philippine

15. Predisposing factors  Race  Deficiency of Protein or carotene  Age- Higher towards the beginning, or end of childbearing age.  HLA-B locus antigen compatibility with Husband  Smoking  Oral contraceptives for more than 5years  H/O infertility

16. Partial Mole  Differs from Complete mole  Morphology  Clinical picture  Pathogenesis  Genetics  Synonyms-Triploidy, partial hydatidiform mole, partial molar pregnancy.  Undiagnosed  Unreported

17.  Partial Mole is common, but unawared, underdiagnosed, and underreported.

18. Importance of Diagnosis 4-12% develop in persistent gestational trophoblastic diseases, and require chemotherapy. Recurrence -3% Chorio-carcinoma-1%

19. Pathogenesis  Two sperms fertilize a single ovum,  Development of certain or all fetal parts  Triploid karyotype of 69XXX, 69XXY, OR 69XYY.  Diploid or tetraploid karyotype may exist.

20. Pathogenesis 69xxx69xxy 69xyy 46xxy

21. Diagnostics in management  Tumor markers  Serum HCG  Alpha feto-protein.  Others like PAPP, Pregnancy specific protein, CA125  Ultrasound examination.  Histo-pathological Analysis.  Genetic Karyotyping, Flow cytometry, ploidy analysis etc.

22. Diagnostic Challenges  Clinical presentation is like normal pregnancy before 12 weeks.  HCG levels may be normal or slightly raised.  USG is usually confusing, specially in first trimester.  Histology is also not conclusive most of the time.

23. Clinical presentation  Symptoms of missed, anembryonic or incomplete abortion  Usually asymptomatic, but may present with hyperemesis gravidarum or pre-eclampsia

24. Human chorionic Gonadotropin  Secreted by active trophoblast of the placenta.  Detected in the blood 7-9 days after ovulation.  A concentration of 100mIU/ml is reached 2 days after the date of an expected menses.  Peak level of HCG ( app. 100,000mIU/ml ) - 10 weeks of gestations  Declining and remaining at app 10,000- 20,000mIU//ml by 12-14 weeks of gestation.

25. Rate of HCG rise Below 1200 IU/LDoubles every 48- 72hrs From 1200 to 6000IU/L Doubles every 72- 96 hrs Above 6000IU/LDoubles every 4 days

26. Diagnostic Implications of Serum HCG levels  Single HCG value –Not very informative  rate of increase in HCG levels varies as a pregnancy progresses.  Normal HCG values vary up to 20 times between different pregnancies,  An HCG that does not double every two to three days does not necessarily indicate a problem with the pregnancy.  Some normal pregnancies will have quite low levels of HCG, and result in perfect babies.

27. Challenges – USG  As the vesicular degeneration is only partial, and delayed, USG findings are not clear as in complete mole.  Gestational sac is not measured routinely.  High resolution Transvaginal USG, and doppler flow study is not available widely.

28. Correlation between HCG level, and sonography findings  Serum HCG levels 1800 IU/L-Gestational sac should be visible by USG  Serum HCG levels 5000IU/L-Cardiac pulsation should be visible.  More than 5000 IU/L rules out Ectopic pregnancy.

29. Serum HCG levels From conceptionFrom LmpIU/L 7days3weeks0to5 14days28days3to426 21days35days18 to 7,340 28days42days1080 to56,500 35-42days49-56days7,650 to 229,000 43-64days57-78days25,700 to 288,200 57-78days79-100days13,300 to 253,000 17-24weeks 2 nd trimester4060 to 65,400 After several days postpartum Non-pregnant levels

30. Diagnostic criteria by USG  Enlarged and cystic placenta with ill-defined fetal echoes, surrounded by a strongly refringent ring.  Transverse diameter is 1.5 times more than of AP diameter.

31. Ultrasonographic D/D  Hydropic degeneration of placenta  Complete mole with co-existent fetus  Leiomyoma of uterus  Retained products of conception  Choriocarcinoma  Missed Abortion  Blighted ovum  Ectopic pregnancy

32. Hydropic Degeneration of placenta  sonographic similarity of a hydropic placenta with marked swelling of the villi to molar tissue.  Vesicles, cysts, fetal remains, and an abnormal placenta can be seen.  The clinical history of the patient -diabetes, isoimmunization, and intragestational infection - should be considered  Beta HCG –Generally lower

33. Hydatidiform Mole with co-existent foetus  Echogenic Intra-uterine tissue that is interspersed with numerous punctuated sonolucencies.  8-12 weeks -Homogenously echogenic intraluminal tissue ( Max. Diam of villi 2mm) with separate normal placenta, and fetus.  18-20 weeks – Cystic spaces ( Max. diam. Of villi 10mm). Molar tissue can cover normal placenta, thus difficult to differentiate from partial mole.

34. Uterine Leiomyoma  Areas of Hyaline degeneration can simulate the appearance of hemorrhage within mole.  Whorled internal consistency distinctly different than Vesicular pattern in mole.  Lack the cystic appearance of mole.

35. RPOC with Hemorrhage  Tissues of mixed echogenicity.  No gestational sac  Vesicular pattern will not be there.  Low levels of HCG.

36. Choriocarcinoma  No Villi  Well-circumscribed echogenic lesion in myometrium

37. Missed Abortions  Echo-refringent and non-homogeneous chorionic tissue remains either located inside the cavity or attached to the uterine wall.  Low or negative hCG levels.

38. Blighted ovum  The perfect interior delimitation of the embryonic sac.  No evidence of any embryo

39. Ectopic pregnancy  Pseudovesicles and a pseudosac  The combined use of quantitative determinations of hCG and vaginal ultrasound may resolve this uncertainty.

40. Histopathology  Two populations of villi  Enlarged villi ( > or= 3-4mm) with central captivation  Irregular villi with geographic, scalloped border with trophoblastic inclusions  Trophoblast hyperplasia, usually focal.

41. Differential histopathology diagnosis  Beckwith-wiedeman syndrome  Twin gestation with complete mole, and co-existent fetus  Early complete hydatidiform mole  Hydropic spontaneous abortion  Placental Angiomatous malformation

42. Cytoflowmetry  Study of DNA content of curetted material.  Confirmation of Diagnosis specially when cofusion in diagnosis, or unnatural behaviour.  For Scientific reports  For research purpose.

43. Serum HCG levels after non trophoblastic Abortions  Should fall to undetectable level by 3 weeks.  Below 5mIUm/l - negative,  Above 25mIU/ml -positive.

44. HCG Levels –after trophoblastic abortions  Greater than 500mIU/ml frequently by 3 weeks and usually by 6 weeks.  HCG titer should fall to a non-detectable level by 15 weeks.

45. HCG levels -Management Indications of chemotherapy  Serum hCG> 20, 000 IU/L at >4 weeks.  Rising hCG. i.e. 2 consecutive rising serum samples.  hCG plateau. i.e. 3 consecutive serum samples not rising or falling significantly.  hCG still abnormal at 6 months post evacuation.

46. Conclusion  Partial Mole is a common, but under-diagnosed gestational trophoblastic disease.  combine use of serum HCG and ultrasonography in early pregnancy leads to suspicion of partial mole, and histology can confirm the diagnosis.  Early diagnosis, and use of prophylactic chemotherapy if indicated can prevent the development of chorio-carcinoma

47. Complete molar pregnancy,

48. USG-Normal Pregnancy  Double Decidual Sign  Intradecidual Sign

49. Blighted Ovum  The perfect interior delimitation of the embryonic sac.  No evidence of any embryo

50. Dr Haseena Hamdani Avicenna Medical Clinic Medswana House, Machel Drive, Gaborone email: hhamdani@rediffmail.com Ph No. +267- 3188808 Cell +267- 71470419 email: hhamdani@rediffmail.com Thank You