Professional Documents
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Ovarian Response
Colin M Howles
Vice President Scientific Affairs
Global Medical Affairs
Merck Serono International SA, Geneva
What I would like to do in
this lecture
ESHRE Capri Workshop Fertility and Aging Hum Reprod Update 2005
Age-related germ cell loss
Germ cells 7
(millions)
6
Baker, 1972
5
1 Birth
0.6
0.3
3 6 9 5 10 20 30 40 50
Months p.c Years
Age
There is a steep decline in the
population of human ovarian
follicles after 35 years of age
106
105
104
Follicular counts
103
102
101
100
0 10 20 30 40 50 60 70 80
Age (years)
Gougeon et al. Biol Reprod 1994 50:653-663
Intervene before FSH driven recruitment phase
What I would like to do in
this lecture
• Ultrasound
♦ Number of antral follicles (AFC), Doppler score (resistance),
ovarian volume
(e.g. Lass et al., 1997; Fratterelli et al., 2000; Popovic-Todorovic et al., 2003; Hansen et
al., 2003; Scheffer et al., 1999, 2003; Van Rooij, 2002; Bancsi, 2003, 2004; Seifer et al
2002; Hansen et al 2003; Muttukrishna et al 2005, Hendriks et al, 2005, 2007; Howles et
al 2006; Kwee et al 2007)
• Hormone levels
♦ Basal FSH, inhibin B, oestradiol, anti-mullerian hormone (AMH)
(e.g. Toner et al., 1991; Scott, 1989, 1996; Fratterelli et al., 2000; Abdallah & Thum,
2004; Seifer, 2002; Rooij, 2002; Eldar-Geva, 2002; de Vet et al 2002; Fanchin, 2003;
Bancsi, 2002, 2003, Akande et al 2002;Laven et al 2004;Hussein 2005; Howles et al
2006; Fleming et al 2006; Kevenaar et al 2007 a,b)
CDC Report for ART in USA; 2006
How do we optimise the response to
ovarian stimulation?
• Take into account specific patient
parameters
• Utilise different stimulation regimens
♦ GnRH antagonist / GnRH agonist
♦ Different gonadotrophin regimens
Meta-analysis including 7 ART studies
comparing r-hFSH vs r-hFSH + r-hLH
(>= 35 yrs)
Therefore:
DOSE = (Y – (α + β 1 AGE + β 2 AGE 2 + β 3 BMI + β 4 FSH + β 5 FOLL_LT11)) / β 6
n 48 45 34 24 10 161
No. cycles 12 4 4 2 2 24
cancelled (%) (25.0) (8.9) (11.8) (8.3) (20.0) (14.9)
Study group
P Barri Rague, A Borini, G D’Amato, D De Ziegler, M Fernandez,
M Germond, T Hahn, JAM Kremer, JSE Laven, M Ludwig,
N Macklon, A Obruca, F Olivennes, T Tanbo, H Tournaye, G Trew,
M Tsirigotis, M Wikland, Y Yang, F Zegers-Hochschild
Expert panel
A Borini (Italy); M Germond (Switzerland); F Olivennes (France);
(G Trew (UK); M Wikland (Sweden); F Zegers (Chile