誘導排卵重要觀念

誘導排卵過程中，連續每日施打中低劑量FSH 75IU 比單獨施打一高劑量375IU
更能達到誘導排卵之效果

誘導排卵過程中，施打FSH劑量不可下降過快造成體內FSH濃度下降過快，對生長中卵泡造成不利影響，甚至 atresia

GnRH agonist flare-up 容易造成卵巢過大水瘤之產生


自然周期療法之試管嬰兒懷孕率仍舊偏低(<20%)


clomid+FSH+GnRHantagonist在溫和誘導排卵過程可達到類似Long protocol+FSH之懷孕率

Clomid缺點: 耗損子宮內膜estrogen receptor

FSH施打劑量過高或血清，E2濃度過高，OHSS可能對卵子染色體與胚胎著床率產生不良影響

低劑量，較溫和之誘導排卵將是未來IVF誘導排卵之主流

http://humupd.oxfordjournals.org/content/15/1/13.full

Figure 1

Schematic representation of life history of ovarian follicles: endowment and maintenance, initial recruitment, maturation, atresia or cyclic recruitment, ovulation, and exhaustion. Adapted from McGee and Hsueh (2000).

Figure 2

(Left) Representation of number and size of antral follicles as assessed by transvaginal ultrasound during the menstrual cycle of a normal cycling woman (Day 0 = LH surge) (Pache et al., 1990).

(Right) Box and whisker plots representing serum FSH (upper panel) and estradiol (lower panel) concentration in 16 regularly menstruating female volunteers, synchronized around the initiation of menses, around the first day of visualization of a dominant follicle, and preceding the mid-cycle LH peak (van Santbrink et al., 1995).

Figure 4

FSH window concept with mild intervention approaches, stressing the significance of the limited duration of FSH elevation above the threshold level rather than the height of the elevation of FSH for multiple dominant follicle selection.

The left figures show the intervention, and the right figures show the resulting number of follicles during the follicular phase in normo-ovulatory female volunteers. (Upper) Natural cycle with single dominant follicle selection. (Middle) Intervention cycle with administration of a single s.c. injection of 375 IU FSH on Day LH+14. (Under) Intervention cycle with five s.c. injections of 75 IU FSH daily from Day LH+19 until Day LH+23. Adapted from Schipper et al. (1998).

Figure 5

Multi-follicular development in normo-ovulatory female volunteers receiving fixed low daily doses (75 IU) of exogenous FSH starting on either CD 3, 5 or 7. The left figures show the intervention, and the right figures show the resulting number of follicles during the follicular phase. Adapted from Hohmann et al. (2001).

Table III

Characteristics of randomized controlled trials involving ovarian stimulation with clomiphene citrate for IVF

Study	Inclusion criteria	Study protocol	Control stimulation protocol	Main outcome
MacDougallet al. (1994)	Patients ≤38 years with >1 year of infertility, spontaneous ovulatory regular cycles and normal semen analysis	CC 100 mg, from Days 2–6, hCG when the leading follicle was 17 mm (n = 16)	Natural cycle IVF with hCG when the leading follicle was 17 mm (n = 14)	Cancellation rate 0 versus 71%. Ongoing pregnancy rate 13 versus 0% (NS)
Dhont et al. (1995)	Patients with no previous IVF attempts. Treatment included IVF-ET, ZIFT and GIFT	OAC pretreatment, CC 100 mg for 5 Days and (150) subsequent HMG (n = 151)	OAC pretreatment, long acting GnRH agonist and (300 IU) HMG (n = 152)	Cancellation rate 20.5 versus 2.6%. Ongoing pregnancy rate 24.5 versus 36.8% (P = 0.02)
Ingerslevet al. (2001)	Couples with no previous IVF attempts under 35 years with ICSI indication, tubal factor or idiopathic infertility	CC 100 mg, from Days 3–7 and hCG when the leading follicle was ≥20 mm (68 patients, 111 cycles)	Natural cycle IVF with hCG when the leading follicle was ≥17 mm (64 patients, 114 cycles)	Cycles resulting in embryo transfer 53.2 versus 25.4%. Ongoing pregnancy rate (per cycle) 18.0versus 3.5% (P < 0.001)
Fiedler et al. (2001) (abstract)	Random selected normal cycling women	100 mg CC CD 5–9, from Day 9 additional 150 IU HMG or FSH. GnRH antagonist from Day 10 (n = 295)	100 mg CC CD 5–9, from Day 9 additional 150 IU HMG or FSH (n = 291)	Ongoing pregnancy rate 23 versus 21% (NS)
Weigert et al. (2002)	Women with no previous IVF cycles, between 20 and 39 years, with normal ovulatory cycles with tubal, male factor or unexplained infertility	OAC pretreatment. CC 100 mg for 5 days in combination with 225 IU of rFSH and 75 IU of rLH on alternate days (n = 154)	Long GnRH suppression and 150 IU rFSH (n = 140)	Ongoing pregnancy rate 35 versus 29% (NS)
Engel et al. (2003)	Healthy female partners of infertile couples, between 18 and 39 years, with regular cycle length. No more than three previous IVF cycles or basal FSH >10 IU/l	Single dose GnRH antagonist protocol. CC 100 mg CD 2–6 of 3–7, CD 6 start 150 IU rFSH (n= 5)	Single dose GnRH antagonist protocol. CC 100 mg CD 2–6 of 3–7, CD 6 start 150 IU HMG (n = 5)	Live birth rate 40 versus 20% (NS)
Lin et al. (2006)	Couples with male-factor infertility who were about to undergo their first ICSI cycle	CC/HMG. Cetrorelix protocol (n= 60)	buserelin long protocol (n = 60)	Pregnancy rate 41.7 versus 40% (NS)