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Nut van AMH dosering in de fertiliteitskliniek

Nut van AMH dosering in de fertiliteitskliniek. Dr. Ellen Anckaert Dienst Klinische Chemie en Radio-immunologie UZ Brussel. Serum AMH. AMH expression in ovarian follicles. Broekmans, Trends Endocrinol Metab 2008.

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Nut van AMH dosering in de fertiliteitskliniek

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  1. Nut van AMH dosering in de fertiliteitskliniek Dr. Ellen Anckaert Dienst Klinische Chemie en Radio-immunologie UZ Brussel

  2. Serum AMH AMH expression in ovarian follicles Broekmans, Trends Endocrinol Metab 2008

  3. Serum AMH is a better predictor of antral follicle count than inhibin B or FSH n = 75 infertile women Fanchin, Hum Reprod 2003

  4. AMH in COH: Study objectives and design Objectives: to investigate • the predictive value of serum and follicular fluid AMH for ovarian response and the occurrence of pregnancy • the effects of COH with HP-hMG and rFSH on AMH levels in serum and in follicle fluid from the largest follicle Design • Exploratory, retrospective analysis of a randomized, assessor-blind, multinational trial (MERIT*) • 731 women undergoing COH for IVF in a long GnRH agonist protocol • HP-hMG (MENOPUR) • rFSH (GONAL-F) • Age 21-37 years, regular menstrual cycles • FSH d3 < 12 IU/l • PCOS excluded • Primary endpoint: ongoing pregnancy rate * Menotropin vs r-FSH IVF trial, Smitz, Hum Reprod 2007

  5. AMH measurements • Blood samples were obtained on day 1 of stimulation (baseline), day 6 of stimulation and last day of stimulation. • Fluid from a follicle  17 mm was collected at oocyte retrieval. • AMH was analyzed at a central laboratory (UZ Brussel) with the Immunotech (Beckman Coulter) immunoassay

  6. Serum AMH (µg/L) Serum AMH by ovarian response to COH Oocytes retrieved p<0.0001 r = 0.530 Basal serum AMH (ng/ml)

  7. Serum AMH correlation with ovarian response after COH

  8. Prediction of poor response Serum AMH and Ovarian response prediction AUC ROC: 0.81 AMH cut-off: 2.8 ng/ml Sensitivity: 70.0% Specificity: 78.0% p < 0.0001 Data are mean + SD

  9. Accuracy of serum AMH for poor response prediction Most studies: AUC ROC 0.80-0.91 AMH is superior to age and/or FSH * Immunotech-Beckman-Coulter assay Broer, Curr Opin Obstet Gynecol 2010

  10. Predictive accuracy of AMH and AFC for poor response after COH AMH AUC: 0.90 AFC AUC: 0.89 Summary ROC curves from meta-analysis, n= 1373 cycles Broer, Curr Opin Obstet Gynecol 2010

  11. Prediction of excessive response Serum AMH by Ovarian response AUC ROC: 0.80 AMH cut-off: 4.6 ng/ml Sensitivity: 68.0 % Specificity: 72.3 % p < 0.0001 Data are mean + SD

  12. Accuracy of serum AMH for excessive response prediction ROC AUC: 0.80-0.92 * Immunotech-Beckman-Coulter assay Broer, Curr Opin Obstet Gynecol 2010

  13. Serum AMH and Ovarian response % Poor response Normal response Hyper response µg/l 16% 56% 28%

  14. Serum AMH declines during COH HP-hMG rFSH AMH (ng/mL) Day 1 4.1 ± 2.5 4.2 ± 2.6 Day 6 3.6 ± 2.2 3.0 ± 1.9 Last day 2.3 ± 1.5 1.9 ± 1.2 * -14.2% * p<0.0001 * -27.5% -46.1% -54.1% Data are mean ± SD

  15. HP-hMG rFSH HP-hMG rFSH p = 0.003 NS NS NS Serum AMH by Ongoing Pregnancy and Embryo Quality Multiple regression analysis: serum AMH is not an independent outcome predictor n = 363 (HP-hMG) and 368 (r-FSH)

  16. NS NS NS NS n = 341 n = 335 Follicular Fluid AMH by Ongoing Pregnancy and Embryo Quality

  17. Follicular fluid AMH in relation to major intrafollicular hormones and to serum AMH FF = follicular fluid from largest follicle at oocyte pick-up

  18. Serum AMH is not an independent predictor of live birth after ART Nelson S, Hum Reprod 2007 ROC analysis: AMH (AUC 0.62) is superior to FSH (AUC 0.42) and age (AUC 0.48); p=0.003. not independent of oocyte yield

  19. Serum AMH: proposed cut-offs for prediction of ovarian response 340 first cycle IVF/ICSI patients Serum AMH measured by DSL ELISA: < 1 pmol/l : cycle cancellation (80%) or  2 oocytes are anticipated 1-5 pmol/l: 41% of women were non- or poor responders 5-15 pmol/l: high probability of normal response > 15 pmol/l: 26 % risk of excessive response ( 21 oocytes at retrieval) ‘Prospective studies are necessary on the concept of individualized and optimized treatment based on AMH prior to first cycle’ Nelson S, Hum Reprod 2007

  20. AMH-based approach to individualization of COH for ART: predicted poor response (AMH 1-5 pmol/l) Reduced treatment burden and cycle cancellation and maintained pregnancy rates Nelson, Hum Reprod 2009

  21. AMH-based approach to individualization of COH for ART: predicted excess response (AMH ≥15 pmol/l) Reduced clinical risk and reduced need for complete cryopreservation Maintained pregnancy rates Nelson, Hum Reprod 2009

  22. AMH immunoassay method comparison Slope = 4 From 2008: Slope = 1 1 µg/l = 7.14 pmol/l !!! Freour, Clin Chim Acta 2007 and UZ Brussel lab data

  23. Clinical utility of AMH measurement: conclusions • AMH is an accurate predictor for poor, but also excessive ovarian response to COH • AMH in serum or follicular fluid is not a good predictive marker for non pregnancy after ART • Intra- and inter-cycle variability of serum AMH is low: one single AMH measurement on any cycle day is sufficient • Large randomized prospective studies are required to confirm that an AMH-based approach to individualization of COH protocols for ART is usefull(Nelson, Hum Reprod 2009) • reduction of clinical risk • optimized treatment burden • cost-benefit ellen.anckaert@uzbrussel.be

  24. Acknowledgements • Ferring Pharmaceuticals A/S, Clinical Research & Development, Copenhagen • Bjarke Mirner Klein • Joan-carles Arce • Lisbeth Helmgaard • Jeppe Voss • Dienst Klinische Chemie en RIA, UZ Brussel • Prof. Dr. Johan Smitz • Johan Schiettecatte

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