Transcript IUI 2011

IUI 2011
Prof. Dr. Esat ORHON
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Ovarian stimulation protocols
(anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists)
for intrauterine insemination (IUI) in women with subfertility (Review)
The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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• Robust evidence is lacking
• Gonadotrophins might be the most effective drugs with IUI
• Low dose protocols are advised
– pregnancy rates do not differ from pregnancy rates which result from
high dose regimen
– the chances to encounter negative effects from ovarian stimulation
such as multiples and OHSS
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Anti-oestrogens
Cost effective but less effective when compared to gonadotrophins.
Do not prevent multiple pregnancies
Have anti-oestrogenic effect on the endometrium
Gonadotrophins
Most effective drugs for IUI
Low dose protocols (50 to 75 IU per day) are advised
Pregnancy rates do not seem to differ significantly from pregnancy rates with high dose regimens (> 75 IU per
day) whereas the changes to encounter negative effects from ovarian stimulation, such as the risk of multiples
and the risk of OHSS might be higher with high dose protocols.
GnRH-agonists
There seems to be no role in IUI programs
Increase costs
Increase multiples without increasing the probability of conception
Urinary gonadotrophins versus Recombinant products
There is no significant difference
GnRH-antagonists
Whether or not are going to play a role in mild ovarian hyperstimulation/IUI programs needs to be determined in
future trials.
Letrozole
There is no convincing evidence that Letrozole is superior to clomiphene citrate and therefore the cost should be
taken into account when using anti-oestrogens.
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Synchronised approach for intrauterine insemination in subfertile couples.
(Review)
The Cochrane Library 2010, Issue 4 Cantineau AEP, Janssen MJ, Cohlen BJ
urinary LH surge versus hCG injection
OR 1.0
95% CI
0.06 to 18)
recombinant hCG versus urinary hCG
OR 1.2
95% CI
0.68 to 2.0)
hCG versus GnRH agonist
OR 1.1
95%
CI 0.42 to 3.1
optimum time interval from hCG injection to IUI No significant differences between
different timing methods for IUI
expressed as live birth rates
All the secondary outcomes analysed showed no significant differences between
treatment groups.
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• There is no evidence to advise one particular treatment
option over another.
• Since different time intervals between hCG and IUI did not
result in different pregnancy rates, a more flexible approach
might be allowed.
• The choice should be based on hospital facilities, convenience
for the patient, medical staff, costs and drop-out levels.
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Soft versus firm catheters for intrauterine insemination (Review)
van der Poel N, Farquhar C, Abou-Setta AM, Benschop L, Heineman MJ
The Cochrane Library 2010, Issue 11
three studies
live birth rates
OR 0.94
95%
CI 0.65 to 1.35)
six studies
clinical pregnancy rates
OR 1.0
95%
CI 0.73 to 1.35 )
two studies
miscarriages
OR 1.25
95%
CI (0.49 to 3.22)
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• There was no evidence of a significant effect difference
regarding the choice of catheter type for any of the outcomes.
• On the basis of the evidence available in this review, no
specific conclusion can be made regarding the superiority of
one catheter class over another.
• Further adequately powered studies reporting on clinical
outcomes (e.g. live birth rate) are required.
• Additional outcomes such as miscarriage rates and measures
of discomfort need to be reported.
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Single versus double intrauterine insemination (IUI) in stimulated cycles for
subfertile couples (Review)
Cantineau AEP, Heineman MJ, Cohlen BJ The Cochrane Library 2010, Issue 11
• six studies involving 1785 women.
• There were no data for the main outcome measure of live
birth per couple or ongoing pregnancy rates, and no authors
presented comparative data for adverse events.
• The results of five studies that reported pregnancy rate per
couple showed a significant effect of using double
insemination
• OR 1.8,
• 95% CI
• 1.4 to 2.4
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• Based on the results of pregnancy rate per couple in five
trials, double intrauterine insemination resulted in significant
benefit over single intrauterine insemination in the treatment
of subfertile couples with husband semen.
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Double versus single intrauterine insemination for unexplained infertility: a
meta-analysis of randomized trials
Nikolaos P. Polyzos, M.D.,a Spyridon Tzioras, M.D., Ph.D.,a Davide Mauri, M.D.,
Ph.D.,a and Athina Tatsioni, M.D., Ph.D.b, Fertil Steril 2010;94:1261–6
• Six randomized trials, involving 829 women, were included in the analysis.
• Fifty-four (13.6%) clinical pregnancies were recorded for treatment with
double IUI and 62 (14.4%) for treatment with single IUI.
• There was no significant difference between the single and double IUI
groups in the probability for clinical pregnancy
– (odds ratio, 0.92; 95% confidence interval, 0.58–1.45; P¼0.715)
• Conclusion: Double IUI offers no clear benefit in the overall clinical
pregnancy rate in couples with unexplained infertility.
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Intra-uterine insemination versus timed intercourse or expectant management
for cervical hostility in subfertile couples (Review)
Helmerhorst FM, Van Vliet HAAM, Gornas T, Finken MJ, Grimes DA
The Cochrane Library 2010, Issue 11
• Each study was too small for a clinically relevant conclusion.
• Only one of the studies provided information on important outcomes such
as spontaneous abortion, multiple pregnancies, but none of studies
reported on the occurrence of e.g. ovarian hyperstimulation syndrome.
• There is no evidence from the published studies that intrauterine
insemination is an effective treatment for cervical hostility.
• Given the poor diagnostic and prognostic properties of the postcoital test
and the observation that the test has no benefit on pregnancy rates,
intrauterine insemination (with or without ovarian stimulation) is unlikely
to be a useful treatment for putative problems identified by postcoital
testing
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Clomiphene citrate for unexplained subfertility in women (Review)
Hughes E, Brown J, Collins JJ, Vanderkerchove P The Cochrane Library 2010, Issue 1
• Data relating to 1159 participants from seven trials were collated.
• There was no evidence that clomiphene citrate was more effective than
no treatment or placebo for live birth (odds ratio (OR) 0.79, 95% CI 0.45 to
1.38; P = 0.41) or for clinical pregnancy per woman randomised both
• with intrauterine insemination (IUI)
– (OR 2.40, 95% CI 0.70 to 8.19; P = 0.16),
• without IUI
– (OR 1.03, 95% CI 0.64 to 1.66; P = 0.91)
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Intra-uterine insemination for unexplained subfertility (Review)
Veltman-Verhulst SM, Cohlen BJ, Hughes E, Heineman MJ, Te Velde E
The Cochrane Library 2010, Issue 11
• In the six trials where IUI was compared with TI, both in stimulated cycles,
there was evidence of an increased chance of pregnancy
– (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50).
• A significant increase in pregnancy rate was also found for women where
IUI with OH was compared with IUI in a natural cycle
– (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71).
• However, the trials provided insufficient data to investigate the impact of
IUI with or without OH on several important outcomes including live birth,
multiple pregnancies, miscarriage and risk of ovarian hyperstimulation.
• There was no evidence of a difference in pregnancy rate for IUI with OH
compared with TI in a natural cycle
– (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87).
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• There is evidence that IUI with OH increases the live birth rate compared
to IUI alone.
• The likelihood of pregnancy was also increased for treatment with IUI
compared to TI both in stimulated cycles.
• There is insufficient data on multiple pregnancies and other adverse
events for treatment with OH.
• Therefore, couples should be fully informed about the risks of IUI and OH
as well as alternative treatment options.
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Cervical insemination versus intra-uterine insemination (Review)
Besselink DE, Farquhar C, Kremer JAM, Marjoribanks J, O’Brien PA
The Cochrane Library 2010, Issue 11
• The search strategy found 232 articles.
• In two studies 134 women had gonadotrophin-stimulated cycles
• In two studies 74 women had clomiphene-stimulated cycles.
• The evidence showed that IUI after 6 cycles significantly improved live
birth rates (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.02 to 3.86)
• pregnancy rates in comparison to cervical insemination. (OR 3.37, 95% CI 1.90
to 5.96)
• There was no statistically significant evidence of an effect on multiple
pregnancies (OR 2.19, 95% CI 0.79 to 6.07)
• or miscarriages
(relative risk (RR) 3.92, 95% CI 0.85 to 17.96).
• The findings of this review support use of IUI rather than CI in stimulated
cycles
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Analysis 1.1. Comparison 1 IUI versus CI in stimulated cycles. Outcome 1 Live birth
rate per woman after all treatment cycles.
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Analysis 1.2. Comparison 1 IUI versus CI in stimulated cycles. Outcome 1 Pregnancy
rate per woman after all treatment cycles.
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Analysis 1.3. Comparison 1 IUI versus CI in stimulated cycles. Outcome 1 Miscarriage
rate per woman after all treatment cycles.
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Analysis 1.4. Comparison 1 IUI versus CI in stimulated cycles. Outcome 1 Multiple
pregnancy rate per woman after all treatment cycles.
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Semen preparation techniques for intrauterine insemination (Review)
Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C
The Cochrane Library 2009, Issue 1
• Five RCTs, including 262 couples in total, were included in the metaanalysis
• No trials reported the primary outcome of live birth.
• There was no evidence of a difference between pregnancy rates (PR) for
swim-up versus a gradient or wash and centrifugation technique,
• nor in the two studies comparing a gradient technique versus wash and
centrifugation.
• There was no evidence of a difference in the miscarriage rate in two
studies comparing swim-up versus a gradient technique.
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• Authors’ conclusions
• There is insufficient evidence to recommend any specific preparation
technique.
• Large high quality randomised controlled trials, comparing the
effectiveness of a gradient and/ or a swim-up and/ or wash and
centrifugation technique on clinical outcome are lacking.
• Further randomised trials are warranted.
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The influence of the number of follicles on pregnancy rates in intrauterine
insemination with ovarian stimulation: a meta-analysis
M.M.E. van Rumste, I.M. Custers, F. van der Veen, M. van Wely, J.L.H. Evers,
B.W.J. Mol. Human Reproduction Update, Vol.14, No.6 pp. 563–570, 2008
• 14 studies reporting on 11 599 cycles.
• The absolute pregnancy rate was 8.4% for monofollicular and 15% for
multifollicular growth.
• The pooled OR for pregnancy after two follicles as compared with
monofollicular growth was 1.6 (99% CI 1.3–2.0),
• whereas for three and four follicles, this was 2.0 and 2.0, respectively.
• Compared with monofollicular growth, pregnancy rates increased by 5, 8
and 8% when stimulating two, three and four follicles.
• The pooled OR for multiple pregnancies after two follicles was 1.7 (99% CI
0.8–3.6),
• whereas for three and four follicles this was 2.8 and 2.3, respectively.
• The risk of multiple pregnancies after two, three and four follicles
increased by 6, 14 and 10%.
• The absolute rate of multiple pregnancies was 0.3% after monofollicular
and 2.8% after multifollicular growth.
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• CONCLUSIONS
• Multifollicular growth is associated with increased pregnancy rates in IUI
with COH.
• Since in cycles with three or four follicles the multiple pregnancy rate
increased without substantial gain in overall pregnancy rate, IUI with COH
should not aim for more than two follicles.
• One stimulated follicle should be the goal if safety is the primary concern,
whereas two follicles may be accepted after careful patient counselling.
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Effects and clinical significance of GnRH antagonist administration for IUI
timing in FSH superovulated cycles: a meta-analysis
Ioannis P. Kosmas, M.D., M.Sc.,a Athina Tatsioni, M.D., Ph.D.,b Efstratios M.
Kolibianakis, M.D., Ph.D.,a Willem Verpoest, M.D.,a Herman Tournaye, M.D.,
Ph.D.,a Josiane Van der Elst, Ph.D., Paul Devroey, M.D., Ph.D.a
Fertil Steril 2008;90:367–72
• Six comparisons were retrieved including 1,069 patients.
• Higher pregnancy rates were found in the randomized controlled trials
(odds ratio [OR] 1.56, 95% confidence interval [CI] 1.05–2.33) when a
GnRH antagonist was added to a gonadotropin superovulated IUI protocol.
• From the randomized controlled trials of this meta-analysis, it is clear that
allowing for follicle growth and avoiding premature LH rise, increased
pregnancy rates are observed with GnRH antagonist administration.
• A parallel trend for multiple pregnancy rates in the GnRH antagonist group
was observed, although this did not reach statistical significance.
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Konuşma Özetleri Kitabı 173
Üreme End. Tek. Cer
IUI 2011
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Prof Dr Esat Orhon
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