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  • 1. AMH - an eligible marker of ovarianfunction for oncological patientsundergoing ovarian tissue bankingMarkus Lipovac, MD*, Gregor Rudelstorfer**, MD,Martin Imhof, MD**General Hospital KorneuburgDepartment for Obstetrics and Gynaecology**Medical University of ViennaDepartment for Gynaecological Endocrinologyand Reproductive Medicine
  • 2. • Chemotherapy with alkylating agents– e.g. Cyclophosphamide• Radiation (LD 50 of the ovary 4 Gy)– bone marrow TX - radiation > 20 GyReduction of Primordial Follicle ReserveMeirow D.; NugentD.: The effects of radiotherapy and chemotherapy on femalereproduction. Hum.Reprod. Update 2001; 7: 535-43
  • 3. Risk estimation of ovarian toxicity of differentchemotherapeutic agentsCyclophosphamidChlorambucilMelphalanBusulfanProcarbazineNitroureaMustinCytosinarabinosidIfosophamidCisplatinAdriamycinEpirubicinMethotrexat5-FluoruracilVincristinBleomycinVinblastinActinomycinOxaliplatinTaxansIrinotecanMonoclonal ABThyrosinkinase-Inhibitorshigh riskunknown riskintermediate risklow riskSonmezer M, Oktay K. Fertility preservation in female patients.Hum Reprod Update 2004; 10: 251–66
  • 4. Damage of Ovarian Structure- impairment of fertility- premature menopauseDue to ovarian damage increasing riskof POF resulting in
  • 5. Ovarian Tissue BankingRestoration of fertility and hormone -production after retransplantation of ovarian tissueCryopreservation of the ovarian tissue (primordialfollicle reserve)Therapy of malignancies e.g.: Leukaemia
  • 6. How to assess the patients ovarian reserveafter completion of the anti-cancer therapy?Ovarian Tissue Banking
  • 7. - Clinical parameters: menospausal symptoms like hotflushes, absence of menstrual bleeding, etc.- Analysis of common ovarian reserve markers like FSH,Inhibin B, EFORTOvarian Tissue BankingAssessment of ovarian reserve
  • 8. AMH – a sensitive marker for ovarian aging- A member of the transforming growth factor-βsuperfamily.- Is produced in the ovary by granulosa cells ofgrowing preantral and small antral follicles.- AMH concentrations correlate well with antral folliclecount and age, and less strongly with inhibin B andFSH levelsDe Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Anti-mullerian hormone serum hormone levels: aputative marker for ovarian aging. Fertil Steril 2002;77:357-362Fanchin R, Schonauer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-mullerian hormone is morestrongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod2003;18: 323-327
  • 9. Question:Is AMH also an eligible marker of ovarianfunction for praemenopausal oncologicalpatients with ovarian cryopreservation?
  • 10. - AMH before and after oncological treatment (patients in remission)out of fresh frozen plasma were measured- Assessment of ovarian function through clinical symptoms ofmenopause- Evaluation of used oncological treatments- Statistical interrelations of AMH before and after oncologicaltreatmentMeasures
  • 11. Results
  • 12. A significant decrease of the AMH-levels of all patients afteroncological therapy could be observedResultsAMH before therapyAMH after therapyvalueinpM
  • 13. - 18 patients out of 74 were analysed- a significant decrease of AMH in all patients wasobserved (p=0,002)- 66% of the patients suffered from POF (p=0,01)- mean AMH before therapy was 15,35 pM(0,01-55,07 pM) and after 1,04 pM (0,01-5,43 pM).Results
  • 14. - Patients who received one cycle ofchemotherapy before OTB showed significantlower AMH-levels (p=0,045)- lower AMH-levels were observed in patientswithout menstruation (p=0,015)- lower AMH-levels were observed in patientsshowing menopausal symptoms (p=0,032) aftertheir oncological treatment.Results
  • 15. - These preliminary data suggets AMH as a proper markerof ovarian function of OTB-patients undergoingoncological therapy- The grade of ovarian damage correlates with the AMH-level- The level of AMH before therapy gives no evidence ofthe individual ovarian outcome of an oncological therapy- More data is necessary to confirm these findings.Conclusion
  • 16. Grazie per la vostra attenzione !!!AMH - an eligible marker of ovarian function foroncological patients undergoing ovarian tissue bankingMarkus Lipovac, MD*, Gregor Rudelstorfer**, MD, Martin Imhof, MD*
  • 17. Low RisikWilms TumorNon-Hodgkin LymphomaHodgkin LymphomaNongenital RhabomyosarkomaOsteosarkomaEpithelialCA of CervixEwing SarkomaKolorectal CAIntermediate RiskBreast CA Stadium I -IIHigh RisikLeukaemiaNeuroblastomaAdenoCA of CervixGenitalRhabdomyosarkomaBreastCA Stadium III-IVAfter: Oktay KH, Yih M: Preliminary experience withorthotopic and heterotopic transplantation ofovarian cortical strips Semin Reprod Med2002,20(1):63-74Frequency of ovarian metastasisOvarian Tissue Banking
  • 18. Ovarian reserve markers in use– Endocrine markers: early FSH, Inhibin B, AMH,different stimulation tests (e.g. clomiphene citrat test,EFORT- exogenous FSH ovarian reserve test )– Ultrasoundmarkers: antral follicle count, ovarianvolume and ovarian perfussion (US)
  • 19. Ovarian Tissue BankingInclusion criteria of the ongoing OTB-Study- Limited patient age: < 37 a- FSH – level < 10- Operation must be possible- No radiation until ovarian tissue withdrawal- Early stage of chemotherapy- Informed consent