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IUI, Ovarian Stimulation and Complications G. I. Serour, FRCOG, FRCS, FACOG (hon) Professor of...
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Transcript of IUI, Ovarian Stimulation and Complications G. I. Serour, FRCOG, FRCS, FACOG (hon) Professor of...
IUI, Ovarian Stimulation and Complications
IUI, Ovarian Stimulation and Complications
G. I. Serour, FRCOG, FRCS, FACOG (hon)Professor of Obstetrics and Gynaecology
Director, International Islamic Center for Population Studies and Research , Al-Azhar University
Clinical Director, The Egyptian IVF-ET Center, Maadi, Cairo, Egypt
FIGO President
04/18/23 1
ERC/ELG
March 3rd-4th, 2012
Items Addressed
04/18/23 2
• What is IUI.
•Indications.
•Effectiveness.
•Cost Effectiveness.
• Factors affecting success rate.
•Advantages and complications.
The rationale behind intrauterine insemination (IUI) with homologous
sperm is bypassing the cervical-mucus barrier and increasing the number of
motile spermatozoa with a high proportion of normal forms at the site
of fertilization.
04/18/23 3
04/18/23 4
This interest in IUI is undoubtedly associated with the refinement of
techniques for the preparation of washed motile spermatozoa.
Semen Preparation Techniques
04/18/23 5
-Swim up.
-Albumin
-Percoll
-Minipercoll
-Glass wool filtration
-Sephadex separation
-Migration sedimentation
-Glass blood separation
04/18/23 6
The washing procedures are necessary to remove
prostaglandins, infectious agents, antigenic proteins, non-motile spermatozoa, leucocytes and immature
germ cells.
04/18/23 7
This may enhance sperm quality by decreasing the formation of
free oxygen radicals after sperm preparation. The final result is an improved fertilizing capacity of the sperm in vitro and in vivo.
Aitken RJ, Clarkson JS et al. Reprod Fertil 1987;81:459-469
Patient preparation
• Natural cycle
• MOH - CC – hCG -CC – hMG –hCG -rec FSH – hCG -GnRH-hMG (rec. FSH) - hCG
Sample for IUI
• Fresh semen • Split ejaculate• Different volumes• Washed semen +/- - Antioxidants - Platelet Activity Factor - Follicular Fluid.
Sites of insemination
• Intrauterine (IUI)
• Intracervical (ICI)
• Intraperitoneal (IPI)
• Cap insemination
• Trans cervical / intrafallopian (ITI)
04/18/23 12
Since IUI programmes are easy to run Cheap and do not need sophisticated equipment IUI is
an attractive choice for the treatment of some infertility
cases in resource poor countries.
It is generally accepted that intrauterine insemination (IUI)
should be preferred to more invasive and expensive techniques
of assisted reproduction and be offered as a first-choice treatment
in some cases of subfertility.
04/18/23 13Ombelet W. et al. hum Reprod, 2008 , doi:10.1093/humrep/den165
Indications • Male factor subfertility• Unexplained infertility• Endometriosis.• Combined ovulatory and ♂ factor
infertility.• Cervical and immunological infertility• Sexual dysfunction infertility.
04/18/23 15
In long standing infertility caused by reduced sperm quality
expectant treatment seems to be disappointing with a spontaneous
conception rate of only 2% per cycle.
Collins J A et al. Fertil Steril; 1995, 64:22-28
Male Factor Subfertility
5th centile 95%CI
Volume 1,5ml (1.4-1.7
P H 7.2
Motility 40% (38-42)
Progressive Non progressive Immotile
32% (31-34)
Vitality (intact membrane)
58% (55-63)
Count 15X106 12-16X10 6
Normal forms 4% (3-4)
04/18/23 16
The lower reference limit for semen analysis
WHO Lab Manual of Human Semen 2010
04/18/23 17
-Oligozoospermia (O)
-Asthenozoospermia (A)
-Tratozoospermia (T)
Male factor Infertility (OAT)
Male subfertility
04/18/23 18
In male subfertility IUI with or without COH a pregnancy rate of 10-18% per cycle has
been reported.
-Stone BA et al 1999. Am. J Obstet Gynecol, 180:1522-1534
- Ombelet W et al 1995,Hum. Reprod. 10 (Suppl. 1):90-120
- Ombelet W et al 1997. Hum. Reprod. 12:1458-1463
Male subfertility
04/18/23 19
A Cochrane review showed that IUI is superior to TI,
both in natural and in cycles with CoH.
Cohlen BJ et al 2000. (Cochrane Review)
Cochrane library, issue 4, update software, Oxford.
04/18/23 20
IUI in natural cycles should be the treatment of choice in case of male
subertility, providing an insemination motile count (IMC) of more than 1 million can be obtained after sperm
preparation and in the absence of a triple sperm defect ( according to WHO
criteria) .
Cohlen BJ et al 2000. (Cochrane Review)
Cochrane library, issue 4, update software, Oxford.
04/18/23 21
IMC and sperm morphology are the most valuable sperm
parameters to predict IUI outcome in male subfertility.
-Ombelet W et al 2003. Reprod Biomed Online 2003;7:485-492
-Duran EH et al , 2002. Systematic Review. Hum. Reprod Update ;8:373-384
04/18/23 22
There is a trend towards increasing conception rates with increasing IMC, but the cut-off value above which IUI seems to be successful, however varies
between 0.3 and 20X106 .-Ombelet W et al 2008. Hum. Reprod. Doi:10.1093/humrep/den165
04/18/23 23
In cases with < 1 million motile spermatozoa, IUI remains
successful provided the sperm morphology score using strict
criteria is 4% or more
(cumulative ongoing PR of 21.9% after three IUI cycles).
-Centole GM 1997. J. Androl; 18:448-453
04/18/23 24
A cut off level of:
0.8 million motile spermatozoa after washing .
Metaanalysis (Van Weert et al 2004 )
30-50% Total sperm motility before sperm preparation
( Ombelet W et al 1996
Dickey et al 1999, Montanaro et al
2001, Lee et al, 2002)
Infertility work -up
No tubal factor
HSG, Laparoscopy, HSCS..
Washing procedure
IMC> 1 millionIMC< 1 million
IMC< 1 million
Morphology <5%
IVF
< 30 % or no fertilization
ICSI
IUI 4x
Proposed algorithm of male subfertility treatment at the Genk Institute for fertility Technology (ICM, insemination motile count of the number of motile spermatozoa after washing procedure; HSG, hysterisalpingography; HSCS, hysatero-salpingo-contrast-sonography)
Ombelet W et al 2008). ESHRE Monograph , 1: 64-72
04/18/23 26
Meta –analysis comparing IUI and TI in natural cycles showed
no difference in results; therefore, IUI in natural cycles seems
ineffective in case of unexplained infertility.
Unexplained infertility
Cohen BJ. Gyn. Obst. Invest; 2005,59:3-13
04/18/23 27
When controlled ovarian hyperstimulation (COH) is
used, IUI becomes effective compared with TI
Cohlen BJ. Gyn. Obst. Invest ;2005;59:3-13
04/18/23 28
There is evidence that IUI with COH increases the live birth rate
compared with IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared with TI in stimulated
cycles. Verhulst SM et al. Cochrane Database Syst Rev 2006;18::CD001838
04/18/23 29
The results of a meta-analysis of randomized controlled trials comparing IUI with timed
intercourse (TI) for couples with cervical factor infertility showed
a significant improved probability of conception for IUI.
Cohlen BJ. Gyn. Obst. Invest ;2005;59:3-13
Cervical Factor Infertility
Sexual Dysfunction infertility
• Retrograde ejaculation• Vaginismus• Hypospadius• Impotence• Infrequent Intercourse during fertile
period.
04/18/23 31
Controversy still surrounds the
effectiveness of this very popular treatment
procedure.
Effectiveness
ESHRE Capri Workshop Group
• Stimulated IUI is ineffective in male infertility and the effect on other diagnoses is small.
• IUI+CC PR 7% /cycle
• IUI+ FSH PR 12 %/ cycle
• IUI+FSH MP 13 %
• Prevention of premature LH | not a major
• Luteal phase support | requirement
04/18/23 32
Crosignani PG et alHum Reprod Update, 2009, vol 15 No. 3, 265-277
04/18/23 33
Treatment Preg. rate per cycle
NNT 95% CI Source or results
IUI 5 32 (12.-46) Guzick et al. (1999), Martinez et al. (1990) and Steures et al. (2007)
CC/IUI* 7 14 (7.-100) Deaton et al. (1990) FSH/IUI 4 -25 (15.-7) Steures et al. (2006) FSH/IUI 12 11 (9.16) Guzick et al. (1999)
IVF 31 4 (3.7) Hughes et al. (2004)
Pregnancy rate per cycle and number needed to treat (NNT)per cycle
*Pregnancy rate per cycle is from Reindollar et al. (2007). NNT is from Deaton et al. (1990) before crossover.
04/18/23 34
ESHRE Capri Workshop Group
IUI in stimulated cycles may be considered while waiting for IVF or when in women with
patent tubes IVF is not affordable.
ESHRE - Hum Reprod. Update, 2009
Vol,15, No. 3, 265-277
04/18/23 35
In most of these indications, IUI or stimulated ovary/IUI is
empiric treatment since it is likely that the majority of
infertility involves factors that are untreatable or unknown.
ESHRE- Hum Reprod. Update, 2009
Vol,15, No. 3, 265-277
• Most studies are retrospective.• Studies vary in: - Comparison of study groups. - Use or non use of MOH. - No of inseminations/treatment cycle. - Different sites of insemination. -Various methods of sperm preparation. - Use/non use of additives as antioxidants,
platelet activation factor (PAF)…etc
Efficacy of IUI
04/18/23 37
Intercourse in natural cycle
IUI in
natural cycle
Intercourse in stimulated cycle
IUI in stimulated cycle
Four comparisons to be performed in RCT to (dis) prove the efficacy of IUI with or without MOH
Cohen BJ and Tournaye H in Macklon NS et al (ed) informa healthcare 2008
IUI / Other modalities
• Success rate • Singleton live birth rate• Cost-benefit analysis• Complication rate• Invasiveness of the technique• Patient compliancy • Healthcare cost
Effectivity has been documented in controlled
studies under the condition that the inseminating motile count exceeds more than 1 million
motile spermatozoa.04/18/23 39
Ombelet W. et al. Hum Reprod, 2008 , doi:10.1093/humrep/den165
Unexplained and moderate ♂ factor subfertility
04/18/23 40
A comparable cumulative ongoing PR after three IUI
cycles for all couples, providing the IMC was more than 1 million was obtained.
- Ombelet W et al 1997. Hum. Reprod. 12:1458-1463
04/18/23 41
Published data comparing cost of IVF versus IUI indicate that initiating treatment with IUI
appeared to be more cost-effective than IVF in most cases of
unexplained and moderate male subfertility
- Ombelet W. et al 2003. Reprod Biomed Online; 7:485-492
- Ombelet W. et al 2005. Hum. Reprod. Update ; 11:3-14
Cost effectiveness
04/18/23 42
In a systematic Review Garceau et al (2002) showed that initially treatment with IUI appears to be more cost-effective than IVF in most cases of unexplained and
moderate male subfertility.
Carceau L et al 2002. Hum Reprod; 17:3090-3109
04/18/23 43
IUI versus IVF
IUI baby
IUI baby
IUI baby
10,000 $
5,000 $
9,500 $
IVF baby
IVF baby
IVF baby
43,000 $
13,000 $
16,000 $
Van Voorhis et al. Fert. Steril 1998
Goverde et al. Lancet 2000
Philips et al. Hum Reprod 2000
Factors affecting IUI success
• Age of the female.• Natural cycle versus MOH• Number of inseminations• Number of IUI treatment cycles. • Site of insemination• Exact timing of IUI• Factors affecting embryos implantation• Laboratory factors
04/18/23 46
Live birth rates could not be assessed
Anti –oestrogens versus gonadotrophins combined with intrauterine insemination outcome: pregnancy rate per couple.
(Contineau AE et al, 2007)
04/18/23 47
One intrauterine insemination (IUI) versus double IUI in stimulated cycles. Outcome: pregnancy rate per couple.
(Contineau AE et al, 2003)
Embryo Implantation
• Endometrial thickness/polyps
• Catheter used
• Us of aspirin and luteal phase support
49
Polypectomy can improve fertility in subfertile women
with asymptomatic
endometrial polyps.Kuohung W & Hornstein M 2010. Up T o Date .
www.uptodate.com
Uterine Polypi
Number and percentage of pregnancies after hysteroscopic polypectomy (n=204) (RCT) 4xIUI
Polypectomy P-value
Study (n=101) Control (n=103)
Pregnancy <0.001
No. 64 29% (63,4) (28,2)RR 2.1 (95% XI 1.5-2.9)
50
Perez –Medina T et al, 2005. Hum Reprod. 20:1632-1635
Laboratory Factors• Sperm washing methods
• Addition of substances in sperm preparation
• Fallopian sperm perfusion
• Effect of abstinence period
• Immunological male subertility
04/18/23 52
•Easy to perform
•Training is easy
•Less invasive
•Risks are minimal
•Quality control possible
•Costs are minimal
Advantage
04/18/23 53
Many studies have shown that appropriate sperm
processing may reduce the risk of HIV, transmission
through IUI and IVF/ICSI.Balet et al 1998, Ohl et al 2005, Manigart et al 2006,
Garrido et al 2002, Savasi et al 2007
04/18/23 54
A Novel washing method combining multiple density
gradients and trypsin for removing HIV and hepatitis C virus from semen seems to be
very promising.
Loskutoff et al 2005.
Huyser et al 2006
Complications • Relatively low success rate / cycle.
• PID 0.01-0.2%.*
• MP
• Prematurity & low birth weight.**
* Dodson and Haney, 1991*Ombelet et al 1995**Wong et al 2002, Gaudoin et al 2003, Ombelet et al 2006.
XX FIGO World Congress of Gyn./ and Obs.
FIGO World Congress 2012 website is now
available at:
56http://www.figo2012.org
IUI versus IVF
04/18/23 58
10,000 $ 43,000 $
IUI baby IVF baby
Van Voorhis et al. Fert. Steril 1998
IUI baby
5,000 $
IVF baby
IVF baby
13,000 $
16,000 $IUI baby9,500 $
Goverde et al. Lancet 2000
Philips et al. Hum Reprod 2000