Frank Vandekerckhove Jaarcongres VVOG Genk, 10 oktober 2013 Plaats van antrale follikelmetingen bij het bepalen van de ovariële reserve Frank Vandekerckhove Jaarcongres VVOG Genk, 10 oktober 2013

Testen ovariële reserve (ORT) Inschatten respons ovariële stimulatie OHSS Lage respons Counseling voorbereiden Individualiseren behandelingsplan Maximaliseren slaagkansen

Vereisten ORT Eenvoudig Betrouwbaar en reproduceerbaar Goedkoop Snel resultaat Onafhankelijk cyclustijdstip Patient compliance

AFC (2D)

A prospective assessment of the predictive value of basal antral follicles in in vitro fertilization cycles John L Frattarelli, MD, Andrew J Levi, MD, Bradley T Miller, MD and James H Segars, MD Fertility and Sterility Volume 80, Issue 2, Pages 350-355 (August 2003) DOI: 10.1016/S0015-0282(03)00664-2

Prospectieve cohort studie N: 289 AFC: 2-10 mm Cancelled: < 3 follikels; E2 < 500 pg/ml

FIGURE 1 Association between antral follicle count (AF) and rates of cycle cancellation and pregnancy. An antral follicle count ≤ 4 was associated with a significant increase in cycle cancellation (41.0% vs. 6.4%) and decrease in pregnancy success in patients without cycle cancellation. Frattarelli. Predictive value of antral follicles in IVF.Fertil Steril 2003.

Voorspellende waarde voor low response Review Voorspellende waarde voor low response Combinatie van ORT (review) versus AFC (2005) ORT: FSH, E2, inhibine B, AMH, AFC, OV, flow, leeftijd, CCCT 11 artikels: 7 cohort 4 case control Slechts 1 studie met zwangerschapscijfers

ROC space with the reported sensitivities and specificities of the multivariate models. ROC space with the reported sensitivities and specificities of the multivariate models. The closed circles represent the estimates from cohort studies whereas the open circles represent the estimates from case–control studies. Furthermore, two summary ROC curves are shown Verhagen T et al. Hum. Reprod. Update 2008;14:95-100

AFC (3D) AFC (3D)

AFC (3D)

Intraobserver and interobserver reliability of automated antral follicle counts made using three-dimensional ultrasound and SonoAVC S. DEB, K. JAYAPRAKASAN, B. K. CAMPBELL, J. S. CLEWES, I. R. JOHNSON and N. J. RAINE-FENNING Ultrasound Obstet Gynecol 2009; 33: 477–483

Observationele studie N: 55 1 performer 3D AVC Analyse off-line P1: 1 X P2: 2 X AFC: 2-10 mm; dag 2-5 Cave: hertellingen

2D 3D 3D AVC

Observationele studie 1 observer AFC: =< 9 mm; dag 2-5 1aire outcome variabele: CPR

The figure shows correlation coefficient (R) and regression coefficient (R2) between 2.1 and 4.0 mm follicles and the total dose of gonadotrophin used, total number of oocytes, number of mature oocytes and number of cleaved embryos. The figure shows correlation coefficient (R) and regression coefficient (R2) between 2.1 and 4.0 mm follicles and the total dose of gonadotrophin used, total number of oocytes, number of mature oocytes and number of cleaved embryos. The correlation between the follicles and the total number of oocytes, mature oocytes and cleaved embryos was significant (P < 0.05); however, did not have significant correlation with the total dose of gonadotrophin. Deb S et al. Hum. Reprod. 2009;24:2124-2132

The figure shows receiver operator characteristic (ROC) curves of different variables predictive of pregnancy on univariate analysis. The figure shows receiver operator characteristic (ROC) curves of different variables predictive of pregnancy on univariate analysis. The area under the curve (AUC) for the antral follicles measuring 2.0–4.0 mm was the maximum (0.694), albeit not significantly different to that of age (0.634), fertilized oocytes (0.633) and cleaved embryos (0.632). Deb S et al. Hum. Reprod. 2009;24:2124-2132

Deb S et al. Hum. Reprod. 2009;24:2124-2132

Review 11 studies OHSS gedefinieerd volgens aantal eicellen, E2, OHSS symptomen AMH cut-off: 1.59-7.00 ng/ml AFC cut-off: 9-18

AMH and AFC in the prediction of an excessive response. AMH and AFC in the prediction of an excessive response. Note: Regardless of the number of cut-offs mentioned per study, only one cut-off was taken into analysis. For the observed values of sensitivity–specificity points, all cut-offs are displayed. Broer S et al. Hum. Reprod. Update 2011;17:46-54

The predictive value of antral follicle count remains unchanged across the menstrual cycle Luk Rombauts, M.D., Ph.D., C.R.E.I., Joseph L. Onwude, M.Sc., Hong W. Chew, M.B.B.S. and Beverley J. Vollenhoven, Ph.D., C.R.E.I. Fertility and Sterility Volume 96, Issue 6, Pages 1514-1518 (December 2011) DOI: 10.1016/j.fertnstert.2011.09.005

Retrospectieve studie N: 3117 Poor response: < 4 eicellen OPU Cave: AFC 19 (IQR 11-31)

Figure 1 Receiver operating characteristic curves (ROCs) for different subgroups. (Top) Cycle day; (middle) endometrial type; (bottom) endometrial thickness.

A characterization of the relationship of ovarian reserve markers with age Mitchell P. Rosen, M.D., Erica Johnstone, M.D., Charles E. McCulloch, Ph.D., Sonya M. Schuh-Huerta, Ph.D., Barbara Sternfeld, Ph.D., Renee A. Reijo-Pera, Ph.D. and Marcelle I. Cedars, M.D. Fertility and Sterility Volume 97, Issue 1, Pages 238-243 (January 2012) DOI: 10.1016/j.fertnstert.2011.10.031

Observationele studie Gezonde personen ORT markers op dag 2-4 Toetsen aan histologische gegevens in dezelfde leeftijdsgroep

Figure 1 Serum markers of ovarian reserve with age.

Review 55 studies Poor response: =< 4 eicellen OPU =< 4 follikels < 12 mm

ROC curves of age and ORT in the prediction of poor response and ongoing pregnancy. ROC curves of age and ORT in the prediction of poor response and ongoing pregnancy. (A) Poor response prediction based on age and ORT. The ROC curves of age or age combined with a single or more ORT are depicted. The ROC curves for ‘Age + AMH’, ‘Age + AMH + AFC’ and ‘Age + AMH + AFC + FSH’ run toward the upper left corner, indicating a good capacity to discriminate between normal and poor responders at certain cut-off levels. (B) Ongoing pregnancy prediction based on age and ORT. The ROC curves age or age combined with one or more ORT run almost parallel to or even cross the X = Y line, indicating that the tests are useless for pregnancy prediction. AFC, antral follicle count; AMH, anti-Müllerian hormone; FSH, follicle stimulating hormone; ORT, ovarian reserve test; ROC, receiver-operating characteristic. Broer S L et al. Hum. Reprod. Update 2013;19:26-36

Biomarkers of ovarian response: current and future applications Scott M. Nelson, Ph.D. Fertility and Sterility Volume 99, Issue 4, Pages 963-969 (March 2013) DOI: 10.1016/j.fertnstert.2012.11.051

Figure 1 Scatter plots and correlations (Pearson correlation coefficients) for log 10 primordial follicle (PF) counts versus ovarian reserve test results. (naar Hansen et al., 2011)

Figure 2 5.6 ng/ml 2.8 ng/ml 0.98ng/ml Antimüllerian hormone (AMH) stratified individualization of treatment as used by the author. Ovarian response categories dictate risk, and treatment strategies are designed to minimize risk while maximizing oocyte yield within each response category. Negligible response means that the conventional criteria for triggering (three follicles ≥17 mm) is unlikely to be achieved. For all antagonist cycles with an excessive response, an agonist trigger is adopted. The AMH measurements are for the AMH Gen II assay, and the values are in pmol/L. The suggested antral follicle count (AFC) thresholds are based on the correlation of AMH and AFC and associated response category literature (30, 65). 0.14 ng/ml

Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good- prognosis patients Joan-Carles Arce, M.D., Ph.D., Antonio La Marca, M.D., Ph.D., Bjarke Mirner Klein, Ph.D., Anders Nyboe Andersen, M.D. and Richard Fleming, Ph.D. Fertility and Sterility Volume 99, Issue 6, Pages 1644-1653.e1 (May 2013) DOI: 10.1016/j.fertnstert.2012.12.048

Herverwerking resultaten RCT: recFSH of urFSH bij antagonisten AFC => 10 Dag 2-3; AFC 2-10 mm Poor response: =< 3 eicellen OPU of onderbreking High response: => 15 eicellen of onderbreking

Figure 1 Box and whisker plots for antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B, and antral follicle count (AFC) at start of stimulation in patients with various numbers of oocytes retrieved after stimulation with highly purified human menopausal gonadotropin (hphMG) or recombinant FSH in a gonadotropin-releasing hormone (GnRH) antagonist protocol. Values are median (lines), 25th–75th percentile (boxes), and 10th–90th percentile (whiskers). hphMG: ≤3 (n = 47), 4–7 (n = 124), 8–14 (n = 145), 15–19 (n = 38), ≥ 20 (n = 18); recombinant FSH: ≤3 (n = 25), 4–7 (n = 112), 8–14 (n = 147), 15–19 (n = 55), ≥ 20 (n = 30).

Figure 2 Receiver operating characteristic (ROC) curve analysis showing the predictive values of antimüllerian (AMH), follicle-stimulating hormone (FSH), inhibin B, and antral follicle count (AFC) at start of stimulation for estimation of poor ovarian response (≤3 oocytes retrieved or cycle cancellation due to poor response) and high response (≥15 oocytes retrieved or cycle cancellation due to excessive response), respectively, after controlled ovarian stimulation in patients treated with highly purified human menopausal gonadotropin (hphMG) or recombinant FSH in a gonadotropin-releasing hormone (GnRH) antagonist protocol. The diagonal line is the reference line of no discrimination (area under the curve = 0.5).

Evaluatie AFC Eenvoudig  Betrouwbaar en reproduceerbaar  Goedkoop Snel resultaat  Onafhankelijk cyclustijdstip Patient compliance 

Evaluatie AFC Eenvoudig  Betrouwbaar en reproduceerbaar  Goedkoop Snel resultaat  Onafhankelijk cyclustijdstip Patient compliance 