Rationale for the use of IUI Vaginal acidity and servical mucus
hostility Concentrated, motile, morphologically normal sperm as
close as possible to the oocytes
Slide 4
Main Indications for IUI 1. Ejaculatory failure 2. Cervical
factor 3. Mild male subfertility 4. Immunological 5. Unexplained
infertility 6. Endometriosis 7. Ovulatory dysfunction 8. HIV
positive male partner and HIV-negative female partner 9. Combined
infertility factors
Slide 5
Assisted reproductive technology in Europe, 2004: results
generated from European registers by ESHRE Andersen et al, Hum
Reprod 2008 Apr From 29 countries, 785 clinics, 367,066 cycles
including: IVF (114,672), ICSI (167,192), frozen embryo (71,997),
egg donation (ED, 10 334), PGD/PGS (2701) and, IVM (170) IUI
115,980 cycles (IUI-H, 98,388; IUI-D, 17,592) No of ET: 1- 19.2%,
2-55.3%, 3-22.1%, 4 or more 3.3% Singleton 77.2 %, twin 21.7%,
triplet 1 % Per Aspiration %Per Transfer % Clinical pregnancy- IVF
26.630.1 Clinical pregnancy- ICSI 27.129.8 IUI-H clin
pregnancy12.6/per cycle
Slide 6
Steps 1. Ovarian stimulation 2. Monitoring of follicular growth
and endometrial development 3. Timing of insemination 4. Semen
preparation 5. IUI with prepared sperm
Slide 7
Factors Affecting Success Rate Cause of infertility Age of both
partners Duration of infertility Treatment cycle rank Sperm
parameters
Slide 8
Clomiphene citrate and intrauterine insemination: analysis of
more than 4100 cycles Dovey S et al, Hum Reprod 2008 Retrospective
cohort study, Boston IVF 4,199 cycles, 1,738 patients, 2002 - July
2007, CC-IUI Under age 35 years cumulative PRs 24.2 % Ages 35-37
18.5 %Ages 38-40 15.1 % Ages 41-42 7.4 %Above 42 1.8 % Younger
patients have a higher PR per cycle than older patients The PR per
cycle for patients who initiate only one or only two treatment
cycles is notably higher than the corresponding per cycle rates for
cycles 3 through 9 The drop in success per patient among 41- and
42-year-olds is sharp, but the exceptionally low success rate above
age 42 suggests that CC with IUI has virtually no place in their
treatment.
Slide 9
Maternal Age An age-related decline in female fecundity has
been documented in women undergoing IUI Successful pregnancy rates
decrease after age 35 and reduce dramatically after age 40 Plosker
et al, Hum Reprod 1994 Tomlinson et al Hum Reprpd 1996
Slide 10
Duration of Infertility The longer the duration of infertility,
the lower the pregnancy rates after IUI The pregnancy rate may be
seriously compromised when infertility has lasted 3 or more years
Nuojua-Huttunen S et al, Hum Reprod 1999 Plosker et al, Hum Reprod
1994 Steures P et al, Fertil Steril 2004
Slide 11
Slide 12
Semen Analysis Characteristics Total motile sperm count > 5
million Kruger morphology 5% Zayed et al, Hum Reprod 1997 Prewashed
semen specimen: More than 4% normal sperm morphology, the chances
of pregnancy after IUI were significantly increased van Waart et
al, Hum Rerprod Update 2001
IUI used for treating male factor infertility has little chance
of success when the; woman is older than 35 years, the number of
motile spermatozoa inseminated is
COST: IVF / IUI Before IVF Cohlen (2005) Gynecol Obstet Invest
Review Cervical factor, male factor (TMS> 10 million),
unexplained infertility Gonadotropins are more effective than CC
Mild ovarian hyperstimulation + IUI is more cost- effective than
IVF
Slide 29
Cost-effectivity in tubal factor infertility MildModerateSevere
Surgery IVFSurgery IVFSurgery IVF 1986 9400 6162 1112516221 14833
Cost-effectivity in endometriosis MildModerateSevere Surgery
IVFSurgery IVFSurgery IVF 2393 9400 8673 11750 34600 19488 Philips,
Hum Reprod, 2000 Cost per pregnancy ()
Slide 30
IUI / IVF: Cost-effectiveness Van Voorhis et al (1998) Fertil
Steril
Slide 31
Slide 32
Slide 33
Outcome: Per live birth-producing pregnancy IVF:12 600
Unstimulated-IUI + IVF:13.100 Stimulated-IUI + IVF:15.100
Hypothetical cohort of 100 couples: Compared with primary offer
IVF, 6 cycles of U-IUI or of S-IUI wolud cost an additional 174.200
and 438.000, representing an opportunity cost of 54 and 136
additional IVF cycles and 14 to 35 live birth-producing pregnancies
respectively
Slide 34
For couples with unexplained and mild male factor subfertility,
primary offer of a full IVF cycle is less costly and more
cost-effective than providing IUI (of any modality) followed by
IVF
Slide 35
Intra-uterine insemination for male subfertility Bensdorp AJ,
Cohlen BJ, Heineman MJ, Vandekerckhove P Cochrane Syst Rev, 2008-1
IUI versus TI both in natural cycles no evidence of difference
(Peto OR 5.3, 95% CI 0.42 to 67) No statistically significant of
difference between pregnancy rates (PR) per couple for IUI + OH
versus IUI could be found (Peto OR 1.47, 95% CI 0.92 to 2.37) IUI
versus TI both in stimulated cycles there was no evidence of
statistically significant difference (Peto OR 1.67, 95% CI 0.83 to
3.37) Conclusion: There was insufficient evidence of effectiveness
to recommend or advise against IUI with or without OH above TI, or
vice versa
Slide 36
Intra-uterine insemination for unexplained subfertility
Verhulst SM, Cohlen BJ, Hughes E, te Velde E, Heineman MJ Cochrane
Syst Revc 2008-1 IUI vs 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 live birth
rate was found for women where IUI with OH was compared with IUI in
natural cycle (four RCTs, 396 women: OR 2.07, 95% CI 1.22 to 3.50).
There is evidence that intra-uterine insemination (IUI) improves
the odds of becoming pregnant for couples with unexplained
subfertility compared to timed intercourse. The addition of
fertility drugs to IUI treatment to induce ovulation also improves
the chances
Slide 37
Ovarian stimulation protocols (anti-oestrogens, gonadotrophins
with and without GnRH agonists/antagonists) for intrauterine
insemination (IUI) in women with subfertility Cantineau AEP, Cohlen
BJ, Heineman MJ Cochrane Syst Rev 2008-1 Forty three trials
involving 3957 women The review compared different drugs for
ovarian hyperstimulation showing that injections result in higher
pregnancy rates compared with oral medication. However, the
evidence for this result is not very strong. This review does not
answer the question whether the addition of GnRH agonist or
antagonist is use ful.
Slide 38
Advantages of IVF over IUI Higher pregnancy rates Knowledge
obtained about fertilization of oocytes Cryopersarvation of spare
embryos Severe male-factor infertility Severe endometriosis Tubal
damage
Slide 39
Should we still perform IUI as IVF-ICSI is promoting so
quickly? All treatment options, side effects, risks and costs
should be discussed with the couples IVF/ICSI is more invasive
Couples should be informed about the real success rates HFB
Slide 40
Conclusion IUI is relatively an effective method of teratment
for certain groups of subfertile couples IUI is less invasive and
cheaper than IVF Careful selection of patients is important Patent
Fallopian tubes No endometriosis of moderate and severe degree No
severe degree of male-factor infertility IVF should be carried out
with couples after 4 cycles