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