Title: Intrauterine insemination: state of the art, 2004
1Intrauterine insemination state of the art, 2004
- Is new always better?
- B.J. Cohlen
- Isala Clinics Zwolle
- The Netherlands
2IUI in 2004
- Introduction
- Strength of evidence
- IUI versus timed intercourse
- Role of mild ovarian hyperstimulation
- Clomiphene or Gonadotropins?
- Prevention of muliplets
- IUI versus IVF-ET or ICSI
- Semen preparation techniques
- Prediction of outcome
3Introduction
Piet Kleine Gold silver medal Olympics
1976 Silver medal Olympics 1980
4Introduction
5Introduction
6Is new always better ?
7Strength of evidence
Ideal large RCTs concealment of
allocation multicenter enough power well
defined population blinding no
drop-outs intention to treat
Reality small trials many retrospective method
of randomization? single center inadequate
power various mixed subpopulations no
blinding many drop outs no intention to treat
8Strength of evidence
- Used
- Systematic reviews
- Meta-analyses
- RCTs only
-
1a
1a
1b
2a
Well designed non randomized controlled trial
2b
Well designed quasi experimental
4
3
Descriptive/cases
Experts
9 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Nat. Cycle and IUI
Nat. Cycle and Intercoure
Stim. Cycle and Intercourse
10 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Nat. Cycle and IUI
Nat. Cycle and Intercoure
11Indications for IUI
- Cervical Hostility
- Male subfertility
- Unexplained subfertility
12 Cervical Hostility, Nat Cy
1a
Glazener 1987 Te Velde 1989 Martinez
1990 Kirby 1991 Check 1995 Total
3.6, 2.0-6.5
0.01 0.1 1 10
Favours timed intercourse favours IUI
13 Male subfertility, Nat Cy
1a
Kerin 1987 Glazener 1987 Ho 1989 Te Velde
1989 Martinez 1990 Kirby 1991 Total
3.1, 1.5-6.3
0.01 0.1 1 10
Favours timed intercourse favours IUI
14Unexplained Subfert., Nat Cy
1a
Martinez 1990 Kirby 1991 Total
2.0, 0.56-6.9
0.01 0.1 1 10
Favours timed intercourse favours IUI
15Natural cycle IUI
Effective in couples with Cervical
hostility Male subfertility Not (proven)
effective in couples with unexplained subf.
1a
1a
1a
16 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Nat. Cycle and IUI
Nat. Cycle and Intercoure
Stim. Cycle and Intercourse
17 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Stim. Cycle and Intercourse
18Male subfertility, Stim Cy
1a
Evans, 1991 Martinez, 1991 Crosignani, 1994 Nan,
1994 Melis, 1995 Gregoriou, 1996 Total
2.1, 1.3 3.5
0.01 0.1 1 10
Favours timed intercourse favours IUI
19Unexplained Subfert., Stim Cy
1a
Crosignani, 1991 Evans, 1991 Martinez,
1991 Karlstrom, 1993 Zikopoulos, 1993 Chung,
1995 Gregoriou, 1995 Melis, 1995 Arcaini,
1996 Total
1.9, 1.4 2.6
0.01 0.1 1 10
Favours timed intercourse favours IUI
20Stimulated cycle IUI
Effective in couples with Male
subfertility unexplained subf.
1a
1a
21 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Nat. Cycle and IUI
Nat. Cycle and Intercoure
Stim. Cycle and Intercourse
22 RCTs to (dis) prove a beneficial effect of IUI
and/or MOH
Nat. Cycle and IUI
23 Male subfertility, IUI
1a
Martinez, 1990 Nulsen, 1993 Arici, 1994 Cohlen,
1998 Goverde, 2000 Total
1.4, 0.86-2.4
0.01 0.1 1 10
Favours natural cycle favours MOH
24 Male subfertility, IUI
1b
RCT, Cohlen, 1998
25 Unexplained subfert, IUI
1a
Martinez, 1990 Murdoch, 1991 Nulsen, 1993 Arici,
1994 Guzick, 1999 Goverde, 2000 Total
2.0, 1.4-2.8
0.01 0.1 1 10
Favours natural cycle favours MOH
26Mild ovarian hyperstimulation
Effective in couples with Mild Male
subfertility Unexplained subfertility
1b
1a
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28Clomiphene or Gonadotrophins
1a
Karlstrom 1993 Balasch 1994 Ecochard
2000 Matorras 1992 Total
2.2, 1.2 3.9
0.01 0.1 1 10
Favours Clomiphene favours Gonadotrophins
29Clomiphene or Gonadotrophins
1a
Gonadotrophins are more effective Also more
cost-effective ? Large multicenter RCT ongoing
in the Netherlands
1b
30 Prevention of multiplets
31Prevention of Multiplets
2b
Statement IUI in combination with MOH is
cost-effective only when the percentage of
multiplets is kept to a minimum
32Prediction of Multiplets
Can we predict the probability of achieving
multiplets?
No firm evidence ! Retrospective studies - age
of the woman - total number of follicles (gt
11 mm) - Estradiol levels For Instance
Tur et al., 2001
2b
33Total follicle numbers (Gleicher et al., 2000)
2b
34Strategy
Subfertile couples after infertility work-up
Mild male subfertility gt 1 year Unexplained
subfert.gt 2 years
Other diagnostic groups Subfertility of a lesser
duration
Start ovarian hyperstimulation with intrauterine
insemination
Different treatment options or expectative
management
1a
1a
Low-dose step-up protocol starting with 50 IU FSH
Or 100 mg CC per day No GnRHa Close monitoring
with ultrasound (and estradiol) andstrict
cancellation criteria
2b
2-3 follicles 15 mm and 4-5 follicles 11
mm and estradiol levels lt 5,000 pmol/L
gt 2-3 follicles 15 mm or gt 4-5 follicles 11
mm or estradiol levels gt 5,000 pmol/L
2b
Cancel cycle - aspiration of
follicles - (conversion to IVF/ET)
2a
Proceed with IUI protocol
35Strategy
Subfertile couples after infertility work-up
Mild male subfertility gt 1 year Unexplained
subfert.gt 2 years
Other diagnostic groups Subfertility of a lesser
duration
1a
Start ovarian hyperstimulation with
intrauterine insemination
Different treatment options or expectative
management
36Strategy
Low-dose step-up protocol starting with 50 IU FSH
or 100 mg CC per day / no GnRHa Close
monitoring with ultrasound (and estradiol) and
strict cancellation criteria
1a/b
2b
2-3 follicles 15 mm and 4-5 follicles 11
mm and estradiol levels lt 5,000 pmol/L
gt 2-3 follicles 15 mm or gt 4-5 follicles 11
mm or estradiol levels gt 5,000 pmol/L
Proceed with IUI protocol
Cancel cycle aspiration of follicles
(conversion to IVF/ET)
2a
37IUI versus IVF
IUI baby
IVF baby
10,000
43,000
1b
Van Voorhis et al. Fertil Steril 1998
38IUI versus IVF
IUI baby
IVF baby
5,000
13,000
1b
Goverde et al. Lancet 2000
39IUI versus ICSI, moderate male SF
IUI baby
ICSI baby
9,500
16,000
2b
Philips et al. Hum Reprod 2000
40Semen Preparation techniques
1a
- Methodological quality of published trials is
extremely low - IUI outcome after Swim-up versus Gradient
techniques - OR with 95 CIs 0.55, 0.17-1.76
- Gradient techniques result in higher recovery
rates - Also higher Pregnancy rates ?
- Cochrane review, Boomsma et al., submitted
41Prediction of outcome
1a
The post-wash TMC can predict non-pregnancy
(cut-off level 0.8-5 million) It does not
predict pregnancy ! Van Weert et al, in press
Sperm morphology is related to IUI outcome (?
4) Van Waart, 2001
42The Future
Prognostic modelling
Validation
Implementation
43The Future
2b
Prognostic model derived from 3,371 couples and
15,000 cycles Negative predictors - increasing
maternal age - longer duration of
subfertility - male factor present -
one-sided tubal pathology - endometriosis -
uterine abnormalities - number of treatment
cycle Favourable predictors - cervical
factor - ovarian hyperstimulation
Steures et al., in press
44The ideal future
Couple with gt 2 year subfertility
Evidence based Fertility work-up
Eimers/Collins Model
IUI prediction Model
IVF / ICSI Model
Spontaneous conception
IUI pregnancy
Prediction of Multiplets
IVF / ICSI pregnancy
Cost-effectiveness per live born baby
45Is new always better ?
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47Is new always better ?
Thank you for your attention