Transcript Document

IUI with gonadotrophins
P Devroey
Centre for Reproductive Medicine
Dutch - speaking Brussels Free University
Laarbeeklaan 101
1090 Brussels Belgium
• Debate is an intellectual game
between friends
• Stimulation of ovulatory women
• Is IUI not an intellectual blunder ?
Intellectual blunder ? Of miskleun ?
• Ovulation induction in anovulatory
women
• Ovarian (superovulation) in IVF
• Ovarian stimulation in ovulatory women
(ovarian enhancement)
Primary endpoint
• Singleton life birth
• (Significant) reduction of multiple
pregnancies
• At present ~
~ 35 children / 100 are
members of a multiple pregnancy
Ovulation enhancement in ovulatory
women (IUI)
Clomiphene citrate
Gonadotrophins
Cheep drug
Expensive drug
Limited monitoring
Extensive monitoring
Limited multiple
pregnancy rate
Substantial multiple
pregnancy rate
(3x higher)
Aanbevelingen voor ovulatie inductie
• Monitoring van clomifeen stimulatie
– Echografische monitoring met hormonale screening op dag 10
is nuttig
– Zuiver echografische screening zonder hormonale screening
kan een alternatief zijn
• Monitoring tijdens stimulatie met gonadotrophines
– Is essentieel om multiple zwangerschappen te voorkomen
– Hormonale bepalingen dag 5 van de cyclus
– Hormonale follow-up om de 2/3 dagen of frequenter
– Echografische follow-up
Werkgroep Reproductieve Geneeskunde VVOG
Ovulation enhancement in ovulatory
women (IUI) (continued)
Clomiphene citrate
Gonadotrophins
Reduced need for selective
follicular aspiration
Substantial need for
selective follicular aspiration
Reduced need for
cancellation
Substantial need for
cancellation
Reduced need for
conversion to IVF
Substantial need for
conversion to IVF
% multiple pregnancies
age
Dickey FS 2001
Strategies to prevent (high order)
multiple pregnancies (IUI)
• Selective follicular aspiration of
supernumerary follicles
– Might be useful in experienced hands
– Needs further investigation in large RCT
– Applicability in non - IVF centers needs
further investigation
Cohlen 2004
Strategies to prevent (high order)
multiple pregnancies (IUI)
• Conversion to IVF
– Suddenly surprise
– Non - informed couples
– Treatment more expensive
– Treatment more invasive
• Conversion to IVF / ET should be discouraged
Cohlen 2004
IUI versus IVF - cost effectiveness
• Goverde
• Karande
• IUI is more cost effective but no costs
for multiple pregnancies !!
Clomiphene citrate versus
gonadotrophins
Small RCT !
Balasch HR 1994
FSH is superior
Matorras HR 2002
FSH is superior
Echocard FS 2000
FSH is not superior
Hughes HR 1997
CC seems less effective
Cohlen Data Base Syst Rev 2002
CC seems less effective
Clomiphene citrate versus
gonadotrophins
“ However large RCTs with sufficient
power to detect clinical relevant
differences in cost effectiveness between
CC and gonadotrophins in IUI cycles
are still lacking”
Cohlen 2004
Current best evidence for advanced
treatment of unexplained subfertility
• There is a call for a large international
factorial study
– No treatment
– CC IUI
– FSH IUI
– IVF
Collins HR 2003
Current best evidence for advanced
treatment of unexplained subfertility
(continued)
• While such a study might cost millions
of dollars, if it is not done many more
millions could be wasted on treatments
that are not as effective as they now
seem
Collins HR 2003
Published data IUI and gonadotrophines
• Male factor infertility (1998 - 2000)
– Pregnancy rate
– Multiple
14 %
12.3 %
• Unexplained infertility (1998 - 2000)
– Pregnancy rate
– Multiple
22 %
20 %
D’Hooghe TG 2002
Published data IUI and gonadotrophines
• Male factor infertility (1994 - 2000)
– Pregnancy rate
– Multiple
12.7 %
15.6 %
• Normospermic group (1994 - 2000)
– Pregnancy rate
– Multiple
21.3 %
15.6 %
Spiessens FS 2003
“ Ovarian stimulation for IUI was
performed either with clomiphene citrate
(CC 50 or 100 mg / d) from day 3 to day
7 of the menstrual cycle (n : 271) or with
hMG (75 or 150 IU / d) from day 2 of
the cycle (n : 601) “
Spiessens D’Hooghe page 1186 FS 2003
“ When women had two or more mature
follicles (> 14 mm) at the time of hCG
injection, selective follicle aspiration was
offered and usually one or two follicles
were kept intact after this procedure“
Spiessens D’Hooghe page 1186 FS 2003
IUI donor
Periode
n
Zwanger
%
UZ Antwerpen
1999 - 2000
351
59
17.0
UZ Gent
1991 - 2003
1275
199
15.6
UZ KUL
1996 - 2002
486
91
18.7
LIFE
1989 - 2000
1821
346
19.0
GIFT GENK
1989 - 2002
398
73
18.7
AZ - VUB
1996 - 2000
442
112
25.4
Clasen (Werkgroep)
Multiple pregnancies - cost
Twins
AZ - VUB
USA
Singleton
6 926 - 51 348 Euro
51 715 US dollar
9 000 US dollar
Infertility therapy - associated multiple pregnancies : an ongoing epidemic
RBM OnLine 2003
Comparison between clomiphene citrate
and gonadotrophins
• Subject of several small RCTs
• Regret fully, the conclusions are
contradictory
Cohlen
Conclusions
IUI is an effective option (10 % pregnancy rate)
If
1 000 000 sperm cells after sperm
preparation
But
lowe dose step-up protocols (50 U)
not withstanding close monitoring
Still
strict cancellation criteria to prevent
multiple pregnancies
Probably in experienced hands selective aspiration
may be an effective alternative
Coda
IUI associated with gonadotrophins treatment
• Invasive
– Follicular aspiration
– Cancellation
– IVF
• Enhance ovulation
• Results in 30 % of children, member of a
multiple pregnancy