1. Mannelijke subfertiliteit Wanneer IUI – IVF of ICSI
Willem Ombelet
Organon has developed recombinant FSH (Puregon, follitropin ), by transfecting Chinese hamster ovary cell lines with plasmids containing the two subunit genes encoding FSH. Puregon is marketed as Follistim in the USA and as Recagon in India. Its generic name is follitropin beta.
Leuven,

2. Mr Charles Kingsland
1st March 2004

3. IUI Indications Cervical factor unexplained Male factor Male factor
immunological
Male factor
mild
Male factor
Moderate to severe

4. When to perform IUI - IVF - ICSI ?
Female age
Costs (couple)
Duration of infertility
Costs (society)
Indication
for fertility Treatment
Complication rate
Sperm quality
Ethics – religion …

5. IUI versus IVF // ICSI: couple compliancy High couple compliancy
Easy
Non-invasive
Minimal risks
Minimal monitoring
Result effective
Cost effective
High couple compliancy

6. Used: Systematic reviews Meta-analyses RCTs only Strength of evidence1b 2a
De kracht van het wetenschappelijk geleverde bewijs kan worden aangegeven met nummering van 1a tot 4, zoals ook in de onlangs gepubliceerde richtlijnen van de RCOG te Engeland. Ik zal zoveel mogelijk gebruik maken van bewijs 1a of 1b.
Well designed non randomized controlled trial 2b
Well designed quasi experimental 3
Descriptive/cases 4
Experts

7. 1a

8. Pregnancy rates as a function of age1b
Goverde et al. Lancet (2000): 355: 13

9. Unexplained and moderate male factor subfertility
IUI versus IVF // ICSI
Unexplained and moderate male factor subfertility
IVF // ICSI versus 3 x IUI
Philips et al., Hum Reprod 15, 95, 2000
Stone et al., AJOG, 180, 1522, 1999
Garceau et al., Hum Reprod 17, 3090, 2002
Cost-benefit

10. IUI versus IVF $ 10,000 $ 43,000 IUI baby IVF baby
IUI versus IVF. De kosten per levend geboren baby in de USA. IUI is evident kosten-effectief.
Van Voorhis et al. Fertil Steril 1998

11. IUI versus IVF $ 5,000 $ 13,000 1a IUI baby IVF baby
Dezelfde conclusie kan worden getrokken in Nederland al zijn wij veel goedkoper.
Goverde et al. Lancet 2000

12. IUI versus ICSI $ 9,500 $ 16,000 IUI baby ICSI baby
Bij mannelijke subfertiliteit: is ICSI beter dan IUI bij een matige mannelijke factor: neen dus.
Philips et al. Hum Reprod 2000

13. IUI : threshold levels for sperm quality IMC
Year
Author
Cycles (n)
COH
IMC
1989
Horvath
451
CC-hMG
> 1
1994
Brasch
1205 -
> 20
1995
Toner
395
FSH, hMG
> 2
1996
Campana
1115
Nat, CC, FSH
Huang
1375
CC, hMG
> 5
Ombelet
1100
> 0.3
1997
Berg
3037
> 0.8
792 CC
> 1 if morph > 4
1998
Van der Westlaken
1763
> 10
1999
Branigan
1160
2000
Stone
9963
Nat, CC, hMG
2001
Khalil
2473
CC,hMG,FSH
Van Voorhis
3479
Nat,CC,hMG
2002
Lee
2846
Ombelet et al., RBM Online, 2003, 7, 485

14. 1a

15. Sperm morphology and IUI
Van Waart et al., Hum Reprod Update, 7, 495, 2001
Structured review – medline search
Threshold value: 4 % (strict criteria)
Odds ratio: (-0.11 to 4.03; p < 0.001)

16. IUI and male factor subfertility
Predictive potential of inseminating motile count (IMC) and sperm morphology
W. Ombelet et al.
Hum Reprod, 12,1458,1997

17. IUI: STIMULATION \ INSEMINATION SCHEDULE
hCG
Clomiphene
5000U
50 mg
MENSES h h 5 6 7 8 9 10 11 X
x+1
x+2 D1
> mm
U.S.
OVARIES
( IUI )
IUI

18. < 1 106 No pregnancy MORPH < 4%
Take Baby Home rate After 3 IUI’s
< 1 106
MORPH < 4%
No pregnancy %
All patients
< 1 106
< 1 106
MORPH >= 4%
All patients
>1 106

19. Algorithm for male subfertility treatment
Tubal Factor
No Tubal Factor
IMC
< 1 million
Morphology < 4%
ICSI
IVF
Morphology >= 4%
>= 1 million
Washing
procedure
IUI 4 x
Initial Semen
Sample
Algorithm for male subfertility treatment
< 30% or no fertilisation

20. 1a

21. PR per cycle: cycle number
PR per cycle: female age

22. In the era of IVF, why IUI? Easier to perform Less invasive
Less expensive
Effective
BUT
major risk: ↑ multiple pregnancy rate

23. 1a

24. 1a

25. Strategies to prevent multiple pregnancies Non-IVF ( IUI )
Natural cycle / Clomiphene citrate
hMG and/or rec FSH: minimal dose step-up regimen
50 IU starting dose + 25 IU increments
Escape IVF
Follicular punction

28. Indications for IVF Tubal infertility and nl / moderate semen quality
IMC > 1 mill & no success after 4-6 IUI’s

29. Indications for ICSI Severe male subfertility :
if IMC < 1.0 mill + Morphology < 4 %
Immunologic male subfertility
Azoospermia (MESA, TESE …)

30. Pros & cons