Upload
imi-kinderwunschklinik
View
130
Download
4
Embed Size (px)
Citation preview
AMH - an eligible marker of ovarian function for oncological patients
undergoing ovarian tissue banking
Markus Lipovac, MD*, Gregor Rudelstorfer**, MD, Martin Imhof, MD*
*General Hospital KorneuburgDepartment for Obstetrics and Gynaecology
**Medical University of ViennaDepartment for Gynaecological Endocrinology
and Reproductive Medicine
• Chemotherapy with alkylating agents– e.g. Cyclophosphamide
• Radiation (LD 50 of the ovary 4 Gy) – bone marrow TX - radiation > 20 Gy
Reduction of Primordial Follicle Reserve
Meirow D.; NugentD.: The effects of radiotherapy and chemotherapy on female reproduction. Hum.Reprod. Update 2001; 7: 535-43
Risk estimation of ovarian toxicity of different chemotherapeutic agents
CyclophosphamidChlorambucil
MelphalanBusulfan
ProcarbazineNitrourea
MustinCytosinarabinosid
Ifosophamid
CisplatinAdriamycinEpirubicin
Methotrexat5-Fluoruracil
VincristinBleomycinVinblastin
ActinomycinOxaliplatin
TaxansIrinotecan
Monoclonal ABThyrosinkinase
-Inhibitors
high risk
unknown risk
intermediate risk
low risk
Sonmezer M, Oktay K. Fertility preservation in female patients.
Hum Reprod Update 2004; 10: 251–66
Damage of Ovarian Structure
- impairment of fertility
- premature menopause
Due to ovarian damage increasing risk
of POF resulting in
Ovarian Tissue Banking
Restoration of fertility and hormone -production after retransplantation of ovarian tissue
Cryopreservation of the ovarian tissue (primordial follicle reserve)
Therapy of malignancies e.g.: Leukaemia
How to assess the patients ovarian reserve
after completion of the anti-cancer therapy?
Ovarian Tissue Banking
- Clinical parameters: menospausal symptoms like hot flushes, absence of menstrual bleeding, etc.
- Analysis of common ovarian reserve markers like FSH, Inhibin B, EFORT
Ovarian Tissue BankingAssessment of ovarian reserve
AMH – a sensitive marker for ovarian aging
- A member of the transforming growth factor-β superfamily.
- Is produced in the ovary by granulosa cells ofgrowing preantral and small antral follicles.
- AMH concentrations correlate well with antral follicle count and age, and less strongly with inhibin B and FSH levels
De Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Anti-mullerian hormone serum hormone levels: a putative marker for ovarian aging. Fertil Steril 2002;77:357-362
Fanchin R, Schonauer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod
2003;18: 323-327
Question:
Is AMH also an eligible marker of ovarian function for praemenopausal oncological patients with ovarian cryopreservation?
- AMH before and after oncological treatment (patients in remission) out of fresh frozen plasma were measured
- Assessment of ovarian function through clinical symptoms of menopause
- Evaluation of used oncological treatments
- Statistical interrelations of AMH before and after oncological treatment
Measures
Results
A significant decrease of the AMH-levels of all patients after oncological therapy could be observed
Results
AMH before therapy
AMH after therapyvalu
e in
pM
- 18 patients out of 74 were analysed
- a significant decrease of AMH in all patients was observed (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
- Patients who received one cycle of chemotherapy before OTB showed significant lower AMH-levels (p=0,045)
- lower AMH-levels were observed in patients without menstruation (p=0,015)
- lower AMH-levels were observed in patients showing menopausal symptoms (p=0,032) after their oncological treatment.
Results
- These preliminary data suggets AMH as a proper marker of ovarian function of OTB-patients undergoing oncological therapy
- The grade of ovarian damage correlates with the AMH-level
- The level of AMH before therapy gives no evidence of the individual ovarian outcome of an oncological therapy
- More data is necessary to confirm these findings.
Conclusion
Grazie per la vostra attenzione !!!
AMH - an eligible marker of ovarian function for oncological patients undergoing ovarian tissue banking
Markus Lipovac, MD*, Gregor Rudelstorfer**, MD, Martin Imhof, MD*
Low Risik
Wilms TumorNon-Hodgkin LymphomaHodgkin LymphomaNongenital RhabomyosarkomaOsteosarkomaEpithelialCA of CervixEwing SarkomaKolorectal CA
Intermediate Risk
Breast CA Stadium I -II
High Risik
LeukaemiaNeuroblastomaAdenoCA of CervixGenital RhabdomyosarkomaBreastCA Stadium III-IV
After: Oktay KH, Yih M: Preliminary experience with orthotopic and heterotopic transplantation of ovarian cortical strips Semin Reprod Med 2002,20(1):63-74
Frequency of ovarian metastasis
Ovarian Tissue Banking
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, ovarian volume and ovarian perfussion (US)
Ovarian Tissue Banking Inclusion 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