1. 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

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

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

7. AFC (2D)

8. 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 (August 2003)
DOI: /S (03)

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

10. 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.

12. 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

13. 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

14. AFC (3D)
AFC (3D)

15. AFC (3D)

16. 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

17. 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

18. 2D 3D
3D AVC

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

21. 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:

22. 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:

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

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

26. 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

27. 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 (December 2011)
DOI: /j.fertnstert

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

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

30. 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 (January 2012)
DOI: /j.fertnstert

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

32. Figure 1
Serum markers of ovarian reserve with age.

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

35. 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

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

37. 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)

38. 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

39. 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 e1 (May 2013)
DOI: /j.fertnstert

40. 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

41. 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).

42. 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).

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

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