Transcript Slide 1

Dr H Faruk Buyru
İÜ İstanbul Medical Faculty
Dept of Obstet&Gynecol
Artificial Insemination
 Homologous artificial insemination
 Heterologous artificial insemination
 Artificial insemination, husband (AIH)
 Artificial insemination, donor (AID)
Rationale for the use of IUI
 Vaginal acidity and servical mucus hostility
 Concentrated, motile, morphologically normal sperm
as close as possible to the oocytes
Main Indications for IUI
1.
2.
3.
4.
5.
6.
7.
8.
9.
Ejaculatory failure
Cervical factor
Mild male subfertility
Immunological
Unexplained infertility
Endometriosis
Ovulatory dysfunction
HIV positive male partner and HIV-negative female
partner
Combined infertility factors
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 pregnancyIVF
26.6
30.1
Clinical pregnancyICSI
27.1
29.8
IUI-H clin pregnancy
12.6/per cycle
Steps
1.
2.
3.
4.
5.
Ovarian stimulation
Monitoring of follicular growth and endometrial
development
Timing of insemination
Semen preparation
IUI with prepared sperm
Factors Affecting Success Rate
 Cause of infertility
 Age of both partners
 Duration of infertility
 Treatment cycle rank
 Sperm parameters
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.
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
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
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
Threshold for IUI > 5X106
W Ombelet et al.. RBM online 2003
Isolated teratozoospermia
Fertil Steril 2008
393 couples, 714 IUI cycles
Prospective observational study
 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 <5 x
10(6),
 normal sperm morphology is <30%
Endometriosis-Related Infertility
Controlled Ovarian Hyperstimulation with Intrauterine Insemination
vs.
In Vitro Fertilization-Embryo Transfer
Dmowski et al., F&S 2002
Endometriosis Conclusion:
 The pregnancy rate achieved by 1 IVF cyle is higher
than cumulative rate of 6 COH-IUI cycles
(independent of age and the stage of disease),
 After 3-4 COH-IUI cycles the success of COH-IUI
does not increase,
 COH-IUI:
 Mild-moderate endometriosis
 < 38 years
IUI-How many cycles?
 489 cycles OI + IUI
 Cycle fecundity rate was 0.07 for the first 4 cycles
 0.03 for the 5-10. cycles
 94% of pregnancies occured in the first four
attemtps
 Remohi et al; Hum Reprod 1989
COH / IUI :
How many cycles?
Cumulative pregnancy rate %
45
40
35
30
25
20
15
10
5
0
1. cycle
2. cycle
3. cycle
4. cycle
5. cycle
Dickey, 2002 F/S
6. cycle
IUI: How many cycles should we perform?
Custers IM et al, Hum Reprod 2008
 Multicentre, retrospective cohort analysis
 Primary outcome: Ongoing pregnancy rate (OPR) per cycle
 3714 couples with male, cervical or unexplained subfertility




underwent 15,303 cycles of IUI.
In 70% of cycles, controlled ovarian hyperstimulation (COH)
was used (51% clomiphene-citrate, 19% gonadotropins).
Mean OPR rate was 5.6% per cycle. OPR in the seventh, eighth
and ninth cycle were 5.1%, 6.7% and 4.6%, respectively.
Taking censored patients into account, the calculated COPR was
18% after the third cycle, 30% after the seventh cycle and 41%
after the ninth cycle.
CONCLUSIONS: OPR in high-order IUI cycles are acceptable,
and do not offer a rationale for cancellation before nine cycles.
Using this type of very mild COH, it may be reasonable to
conduct up to nine cycles.
Comparison
 Success rates
 Cost-benefit analysis
 Complication rates
 The invasiveness of the techniques
 Couple compliance
Cost
 Initiating treatment with IUI appeared to be more
cost-effective than IVF most cases of unexplained
and moderate male subfertility
 Goverde AJ et al, Lancet 2000
 Karande VC et al, Fetil Steril 1999
 Philips Z et al, Hum Reprod 2000
 Van Voorhis BJ, Fertl Steril 1998
 Nuojua-Huttunen S et al; Hum Reprod 1999
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 costeffective than IVF
Cost per pregnancy (£)
Cost-effectivity in tubal factor infertility
Mild
Surgery
1986
IVF
9400
Moderate
Surgery IVF
Severe
Surgery
6162
16221
11125
IVF
14833
Cost-effectivity in endometriosis
Mild
Surgery
2393
IVF
9400
Philips, Hum Reprod, 2000
Moderate
Surgery IVF
Severe
Surgery
8673
34600
11750
IVF
19488
IUI / IVF: Cost-effectiveness
Van Voorhis et al (1998) Fertil Steril
IUI / IVF: Cost-effectiveness
Van Voorhis et al (1998) Fertil Steril
 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
 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
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
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
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
useful.
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
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
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
Teşekkür ederim