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Human Reproduction 2008 doi:10.

1093/humrep/den165

Intrauterine insemination (IUI) as a first-line treatment in


developing countries and methodological aspects that might
influence IUI success

Willem Ombelet1,2,4, Rudi Campo1,3, Eugene Bosmans1 and Martine Nijs1


1
Genk Institute for Fertility Technologies, Department of Obstetrics and Gynaecology, Ziekenhuizen Oost-Limburg, Schiepse Bos 2,
3600 Genk, Belgium; 2Flemish Society of Obstetrics and Gynaecology, Belgium; 3Leuven Institute for Fertility and Embryology,
Leuven, Belgium
4
Correspondence address. E-mail: willem.ombelet@telenet.be

It is generally accepted that intrauterine insemination (IUI) should be preferred to more invasive and expensive tech-
niques of assisted reproduction and be offered as a first-choice treatment in cases of unexplained and moderate male
factor subfertility. Scientific validation of this strategy is rather difficult because literature is rather confusing and not
conclusive. IUI is proven easier to perform, less invasive and less expensive than other methods of assisted reproduc-
tion. Effectivity has been documented in controlled studies under the condition that the inseminating motile count
exceeds more than 1 million motile spermatozoa. Risks are minimal, provided the multiple gestation incidence can
be reduced to an acceptable level and provided at least one tube is patent. Therefore, in developing countries, reflec-
tion on the implementation and use of IUI as a first-line treatment for most cases of non-tubal infertility seems
mandatory. The costs are minimal, training is easy, quality control possible and severe complications are almost
non-existing. In cases of unexplained infertility or combined male subfertility and ovulatory dysfunction, correction
and/or ovarian stimulation with clomiphene citrate (CC) is probably the best strategy from a cost –benefit point of
view unless CC-resistancy has been proven in which the use of low-dose gonadotrophins is necessary.

Keywords: affordable; assisted reproduction; cost-effectiveness; developing countries; intrauterine insemination

Introduction This may be explained by the fact that most studies are retro-
The rationale behind intrauterine insemination (IUI) with hom- spective and not only vary in the comparison of the study
ologous sperm is bypassing the cervical – mucus barrier and group but also in the use or non-use of different ovarian super-
increasing the number of motile spermatozoa with a high pro- ovulation regimen, the number of inseminations per treatment
portion of normal forms at the site of fertilization. A few cycle, different methods of timing ovulation, different sites of
decades ago, homologous artificial insemination was only per- insemination, various methods of sperm preparation and the
formed in cases of male subfertility and psychologic dysfunc- well or not use of additives such as antioxidants,
tion, such as retrograde ejaculation, vaginismus, hypospadias platelet-activating factor (PAF), etc (Fig. 1).
and impotence. With the routine use of post-coital tests, other If IUI is promoted as a first-line treatment in case of
indications were added such as hostile cervical mucus and unexplained and male factor subfertility, it has to be weighed
immunologic causes. This interest in IUI is undoubtedly against other treatment options such as expectant management,
associated with the refinement of techniques for the preparation medical and surgical treatment, IVF and ICSI. This comparison
of washed motile spermatozoa. These washing procedures are should not only involve success rates but should also include a
necessary to remove prostaglandins, infectious agents, anti- cost– benefit analysis, an analysis of the complication rate
genic proteins, non-motile spermatozoa, leucocytes and imma- of the different treatment options, the invasiveness of the
ture germ cells. This may enhance sperm quality by decreasing techniques and patient compliancy.
the formation of free oxygen radicals after sperm preparation. Healthcare cost consciousness has become an integral part in
The final result is an improved fertilizing capacity of the the attitude of policy makers worldwide. Evidence related to
sperm in vitro and in vivo (Aitken and Clarkson, 1987). the cost and effectiveness of infertility treatment exists, but
From a scientific point of view, controversy still surrounds most studies only deal with IVF. Published data comparing
the effectiveness of this very popular treatment procedure. cost of IVF versus IUI indicate that initiating treatment with

64 # The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
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IUI as a first-line treatment in developing countries

Figure 1: Diagram showing the many different variables influencing success rates in IUI programmes (AIH, artificial insemination with hom-
ologous semen).

IUI appeared to be more cost-effective than IVF in most cases couples with cervical factor infertility showed a significant
of unexplained and moderate male subfertility (Ombelet et al., improved probability of conception for IUI (Cohlen, 2005).
2003; Ombelet, 2005). Surprisingly and despite evidence-
based arguments, data from Australia and New Zealand Unexplained subfertility
clearly show that almost 80% of fertility centres are convinced If an infertility work-up is unable to detect a plausible expla-
of the cost-effectiveness of IUI, but nearly one-third of these nation for couples with a history of subfertility of at least 1
centres still promote IVF as a first-line treatment even with year, we use the term ‘unexplained infertility’. Because a
patent tubes and normal semen (Miskry and Chapman, 2002). good explanation for the subfertility is lacking, the treatment
Since IUI programmes are easy to run, this method can be is often empiric. A meta-analysis comparing IUI and TI in
extremely interesting for resource-poor countries. The tech- natural cycles showed no difference in results; therefore, IUI
niques and methods are easy to learn, the direct and indirect in natural cycles seems ineffective in case of unexplained
costs are minimal compared with IVF/ICSI and severe compli- infertility. When controlled ovarian hyperstimulation (COH)
cations are very rarely seen. The use of affordable and safe is used, IUI becomes effective compared with TI (Cohlen,
washing techniques and the value of natural cycle or clomi- 2005). There is evidence that IUI with COH increases the
phene citrate (CC) stimulation also adds to the value of IUI live birth rate compared with IUI alone. The likelihood of
in developing countries. pregnancy was also increased for treatment with IUI compared
The topics highlighted in this paper are summarized in with TI in stimulated cycles (Verhulst et al., 2006).
Table I.
Male factor subfertility
In case of longstanding infertility caused by reduced sperm
quality, expectant treatment seems to be disappointing with a
Effectiveness of IUI
spontaneous conception rate of only 2% per cycle (Collins
Cervical factor subfertility et al., 1995). Therefore, this strategy is not applicable in clini-
Bypassing the hostile cervix should increase the probability of cal practice. For IUI, with or without COH, a pregnancy rate
conception. The results of a meta-analysis of randomized con- (PR) of 10– 18% per cycle has been reported (Ombelet et al.,
trolled trials comparing IUI with timed intercourse (TI) for 1995, 1997a; Stone et al., 1999). A Cochrane review showed
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Ombelet et al.

Cost of ART-related services


Table I. Summary of topics highlighted in this paper.
In a meta-analysis, Peterson et al. (1994) showed that the PR
† Introduction for three cycles of gonadotrophins and IUI in a population
† Effectiveness of IUI
Cervical factor subfertility group with unexplained infertility was superior to IVF and
Unexplained subfertility comparable with gamete intra-Fallopian transfer. Many other
Male factor subfertility studies reported on the cost-effectiveness of IUI compared
† Cost of ART-related services
† Risks and complications of IUI versus IVF/ICSI with IVF (Van Voorhis et al., 1997, 2001; Zayed et al.,
† Couple compliancy 1997). In a prospective randomized controlled trial, Goverde
† Treatment strategy in developing countries: a proposal et al. (2000) concluded that three cycles of IUI offer the
† Factors influencing IUI success
Natural cycle versus controlled ovarian hyperstimulation same likelihood of a successful pregnancy as one trial of
Site of insemination IVF. They concluded that IUI is a more cost-effective
Exact timing of IUI approach, not only for unexplained subfertility, but also for
Factors affecting embryo-implantation
) Endometrial thickness/polyps moderate male factor subfertility. This important message
) Which catheter to use was confirmed in another study performed in the UK (Philips
) The use of aspirin and luteal phase support et al., 2000). In this study, the authors complemented existing
Laboratory factors
) Sperm washing methods clinical guidelines by including cost-effectiveness of different
) Addition of substances in sperm preparations treatment options for infertility in the UK. A series of
) Fallopian sperm perfusion decision-analytical models were developed to reflect current
) The effect of the abstinence period
) Immunologic male subfertility diagnostic and treatment pathways for the different causes of
Number of inseminations infertility. According to this study, stimulated IUI for unex-
Number of IUI treatment cycles plained and moderate male factor infertility is a cost-effective
† Conclusion
approach. In a systematic review, Garceau et al. (2002) also
showed that initiating treatment with IUI appears to be more
cost-effective than IVF in most cases of unexplained and mod-
that IUI is superior to TI, both in natural cycles and in cycles erate male subfertility. For couples with unexplained and mild
with COH (Cohlen et al., 2000). According to this review, male factor subfertility, Pashayan et al. (2006) showed that
IUI in natural cycles should be the treatment of choice in primary offering a full IVF cycle was less costly and more
case of male subfertility, providing an inseminating motile cost-effective than providing IUI followed by IVF. In their
count (IMC) of more than 1 million can be obtained after mathematical model, the assumed LBR (live birth-producing
sperm preparation and in the absence of a triple sperm defect pregnancy) was only 3% for CC-stimulated IUI and 7% for
(according to WHO criteria). gonadotrophin-stimulated IUI, although most centres world-
In the selection of couples to be treated with IUI, it would be wide have a significantly higher LBR (Ombelet et al., 2003).
interesting to establish cut-off values of semen parameters This might explain the opposite findings in their study.
above which IUI is a real alternative for IVF/ICSI in male
subfertility. According to the literature, IMC and sperm
morphology are the most valuable sperm parameters to
predict IUI outcome (Duran et al., 2002; Ombelet et al., Risks and complications of IUI versus IVF/ICSI in
2003). There is a trend towards increasing conception rates developing countries
with increasing IMC, but the cut-off value above which IUI Transmission of life-threatening sexually transmitted diseases,
seems to be successful, however, varies between 0.3 and infectious diseases such as HIV, HCV and Hepatitis B, consti-
20  106. A large retrospective analysis in a selected group tutes particular risk in developing countries since these diseases
of patients with normal ovarian response to clomiphene (CC) may be highly prevalent in subfertile couples. It is estimated
stimulation showed a comparable cumulative ongoing PR that nearly 40 million people worldwide are infected with
after three IUI cycles for all couples, providing the IMC was HIV and prevalence among young people under age of 25
more than 1 million (Ombelet et al., 1997a). Furthermore, years account for approximately half of all new infections
in cases with ,1 million motile spermatozoa, IUI remains (Sauer, 2005). Most HIV patients are of reproductive age and
successful provided the sperm morphology score using strict many desire to have children. Many studies have shown
criteria is 4% or more (cumulative ongoing PR of 21.9% that appropriate sperm processing may reduce the risk of
after three IUI cycles). Acceptable PR can be achieved with HIV transmission through IUI and IVF/ICSI (Balet et al.,
IUI, even in severely oligozoospermic men (Centola, 1997). 1998; Ohl et al., 2005; Manigart et al., 2006; Garrido et al.,
A significant improvement in PR was reported when the 2006; Savasi et al., 2007). Sperm washing techniques appear
morphology score was more than 5% using strict criteria in a to be relatively safe and effective, offering HIV-serodiscordant
meta-analysis by Van Waart et al. (2001). A cut-off level of and couples where both partners are infected an opportunity
0.8 million motile spermatozoa after washing was reported in to have children, provided antiretroviral therapy and HIV
a meta-analysis by van Weert et al. (2004). For total sperm monitoring are available. The challenges created by the HIV
motility before sperm preparation, cut-off levels vary epidemic versus reproductive desires and health needs of a
between 30% and 50% (Ombelet et al., 1996; Dickey et al., large HIV infected population are well described elsewhere
1999; Montanaro et al., 2001; Lee et al., 2002). in this monograph (Dyer et al; this monograph).
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IUI as a first-line treatment in developing countries

In this context, semen decontamination through sperm pro- and minimal dose regimen with gonadotrophins are valuable
cessing is very important in countries with a high rate of options to prevent the unacceptable high multiple gestation
seminal infection, since IUI and ART may become important rate described after ovarian hyperstimulation.
tools, not only in the recognition of the reproductive rights of Considering obstetric and perinatal outcome after IUI, to our
HIV-infected parents but also in the prevention of the trans- knowledge only four papers have been published. According to
mission of HIV among partners and towards the fetus. Nuojua-Huttunen et al. (1999) and using the data obtained from
The use of a novel washing method combining multiple the Finnish Medical Birth Register, IUI treatment did not
density gradients and trypsin for removing human immuno- increase obstetric or perinatal risks compared with matched
deficiency virus-1 and hepatitis C virus from semen seems spontaneous or IVF pregnancies. The three other studies
to be very promising (Loskutoff et al., 2005; Huyser et al., observed a higher risk for prematurity and (very) low birth
2006). weight for IUI singletons when compared with naturally con-
Ovarian hyperstimulation syndrome (OHSS) may compli- ceived singletons (Wang et al., 2002; Gaudoin et al., 2003;
cate all methods of treatment in which gonadotrophins are Ombelet et al., 2006).
used; however, OHSS seems to be rare after COH – IUI com-
pared with IVF due to the fact that lower dose stimulation pro-
tocols are more often used (Dodson and Haney, 1991; Bergh
and Lundkvist, 1992; Ombelet et al., 1995). The incidence of Couple compliancy
pelvic inflammatory disease after intrauterine catheterization Since IUI is a simple and non-invasive technique, it can be per-
and/or transvaginal oocyte-aspiration has been estimated to formed without expensive infrastructure with a good success
be 0.2% for IVF (Bergh and Lundkvist, 1992) and 0.01– rate within three or four cycles, making this method of assisted
0.2% for IUI (Dodson and Haney, 1991; Ombelet et al., reproduction very appealing for developing countries. On the
1995). The major complication of assisted reproductive tech- other hand, we have to admit that in some areas, such as sub-
nology remains, however, the high incidence of multiple preg- Saharan Africa, the majority of patients suffer of tubal factor
nancies, responsible for considerable mortality, morbidity and infertility. In these cases, only IVF can be proposed.
costs (Ombelet et al., 2005). The prediction of multiple ges- Nevertheless, IUI is a safe and easy treatment with minimal
tation is highly uncertain, especially when gonadotrophins risks and monitoring, at least if multiple PR can be avoided.
are used, despite careful monitoring of the cycle with ultraso- Subsequently, a high couple compliancy is reported for IUI
nography and serum estradiol determinations. Careful monitor- compared with IVF. We previously described a low dropout
ing remains essential and cancellation of the insemination rate of 19.6% in a series of 1100 IUI cycles (Ombelet et al.,
procedure, escape IVF and follicular aspiration before IUI 1996). A much higher dropout rate and long time interval
are reasonable options. Transvaginal ultrasound-guided aspira- between treatment cycles for IVF and ICSI have been
tion of supernumerary ovarian follicles increases both the effi- described before (Comhaire, 1995). It is obvious that IUI
cacy and the safety of COH – IUI with gonadotrophins (De must be considered as a very important first-line treatment in
Geyter et al., 1998; Albano et al., 2001). This method rep- selected cases in developing countries.
resents an alternative for conversion of overstimulated cycles Table II gives an overview of the pros and cons of IUI com-
to in vitro fertilization (escape IVF). Natural cycle IUI, CC pared with IVF/ICSI.

Table II. Overview of the pros and cons of IUI compared with IVF and ICSI.

PROS CONS

IUI † Less equipment necessary † + success-rate per cycle


† Easy method: less complex † + success if IMC,1 million
† Less invasive: more physiological † + success if morphology,5%
† Less expensive † High MPR with gonadotrophins
† Reduced psychological burden † Risk for antisperm antibodies
† Good couple compliancy ) low dropout rate
† Low risk for OHSS, thrombo-embolism
† Low to moderate MPR with NC, CC and low-dose gonadotrophin protocols
IVF/ICSI † Minimal transmission of infection (IVF) † High costs (direct and indirect)
† Moderate to high success-rate per cycle † Complex stimulation protocols
† * patient discomfort
† Time-consuming
† Invasive procedure
† * risk for OHSS, thrombo-embolism
† High multiple pregnancy rate
† * Risk for LBW, prematurity
† * Risk for genetic disorders
† Lower couple compliancy
) High dropout rate

IMC, inseminating motile count; OHSS, ovarian hyperstimulation syndrome; NC, natural cycle; CC, clomiphene citrate; LBW, low birth weight (,2500 g);
MPR, multiple pregnancy rate.

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Treatment strategy in developing countries: a proposal Natural cycle versus controlled ovarian hyperstimulation
Figure 2 shows the treatment strategy used for more than 10 Poor results have been described when IUI was performed in
years at the Genk Institute for Fertility Technology. In most natural cycles for unexplained and cervical factor subfertility
cases, we start with CC ovarian stimulation, although the (DiMarzo et al., 1992; Ombelet et al., 1995). The rationale
cumulative ongoing PR is significantly lower compared with behind the use of ovarian hyperstimulation in artificial insemi-
rec-FSH or (purified) urinary gonadotrophins, but with the nation is the increase of the number of oocytes available for
benefit of a low multiple PR (,7%) because of intensive moni- fertilization and to correct subtle unpredictable ovulatory
toring of the number of follicles. If more than three follicles dysfunction (Arici et al., 1994).
with a mean diameter of .13 mm are present, the cycle is can- Comparing the effect of COH on PR after IUI, ovarian
celled (Ombelet et al., 1996). Although the cumulative ongoing stimulation with gonadotrophins or rec-FSH results in a signifi-
PR after three IUI cycles is comparable with only one IVF cantly higher monthly fecundability compared with CC treat-
cycle (25%), more than 90% of our couples agree to follow ment, but at the expense of a higher multiple PR (Ombelet
our protocol being aware of the better success rate per cycle et al., 1995, 1996). This statistical difference is not influenced
after IVF. Excellent counselling is mandatory and crucial. by the indication for IUI. Considering the risk for multiple
The strategy of using CC – IUI as a first-line treatment in pregnancies and OHSS, mild COH regimen with the aim of
most cases of non-obstructive subfertility (male and female) monofollicular growth should be used. The aromatase inhibitor
is of outstanding importance for developing countries. letrozole and CC are associated with similar PR in IUI
(Al-Fozan et al., 2004). The ideal dose of letrozole remains
unknown, and further studies are needed. Since letrozole is
Factors influencing IUI success more expensive than CC, we still believe that the use of
CC – IUI is the best option in developing countries, at least in
The duration of subfertility, primary or secondary subfertility,
the absence of bilateral tubal block and CC resistancy.
endometriosis and the use or non-use of ovarian hyperstimula-
tion are important factors influencing the success rate of IUI sig- Site of insemination
nificantly (Crosignani and Walters, 1994; Steures et al., 2004).
Artificial inseminations can be done intravaginally, intracervi-
Other variables might be the site of insemination, the use of
cally (ICI), pericervically using a cap, IUI, transcervical
antioxidants, factors influencing intra-tubal environment and
intrafallopian (IFI) or directly intraperitoneal (IPI). Most
factors influencing embryo implantation (Iberico et al., 2004).
studies refer to IUI, which seems to be an easy and better
way of treatment. In a donor insemination programme, Hurd
et al. (1993) reported a significantly better cycle fecundity
rate for IUI compared with ICI or IFI. More sperm was
found in the peritoneal cavity after IUI when compared with
ICI (Ripps et al., 1994). Studies comparing pregnancy
outcome after IUI versus cervical cap insemination (Williams
et al., 1995) and transuterotubal insemination (Oei et al.,
1992) also favoured the intrauterine method. In a large random-
ized controlled trial, it was shown that among infertile couples,
treatment with induction of superovulation and IUI is three
times as likely to result in pregnancy as is intracervical insemi-
nation and twice as likely to result in pregnancy as is treatment
with either superovulation and intracervical insemination or
IUI alone (Guzick et al., 1999).

Exact timing of IUI


Exact timing is probably crucial in IUI treatment cycles. On the
other hand, conflicting data are reported in the literature on
which methodology is to be used. Ultrasound and hormonal
monitoring with human chorionic gonadotrophin (hCG) induc-
tion probably allows the most exact timing but is relatively
expensive and time-consuming. Urinary luteinizing hormone
(LH) timed IUI is commonly used but has the disadvantage
that the LH surge can last for up to 2 days before ovulation
in some patients (Cohlen et al., 1993). A prospective, random-
ized cross-over study of Zreik et al. (1999) could not demon-
Figure 2: Proposed algorithm of male subfertility treatment at the strate an increased PR when ultrasound monitoring and hCG
Genk Institute for Fertility Technology (IMC, inseminating motile
count or the number of motile spermatozoa after washing procedure; were used compared with urinary LH-timed inseminations.
HSG, hysterosalpingography; HSCS, hystero-salpingo-contrast- In a prospective randomized study (Lewis et al., 2006), all
sonography). patients received CC and were randomized into a LH
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IUI as a first-line treatment in developing countries

(urinary LH) surge group or a follicle monitoring/hCG group. raw semen sample is used for IUI. The preparation will concen-
Patients in the LH surge group underwent IUI on the day after a trate morphologically more normal and motile spermatozoa,
home test for the LH surge was positive, whereas those in the essential for good results in IUI. Most popular are the
hCG group received hCG according to ultrasound parameters swim-up procedures, the density gradient centrifugation and
and underwent insemination 33– 40 h later. Similar results the use of Sephadex columns. Conflicting data are found on
were found between groups in PR per patient or per cycle. the superiority of any one preparation technique in terms of
After ovarian stimulation with CC, IUI is equally effective fecundity (Dodson et al., 1998; Ren et al., 2004). This can be
24 h after a spontaneous LH surge or 36 h after administration explained by the fact that almost all methods of sperm
of hCG (Vlahos et al., 2005). washing and preparation surpasses the low threshold number
It seems that being aware of the importance of exact timing of motile spermatozoa (.1 106) needed for conception
is essential in IUI, independent of the method being used. In in vivo with no added benefit of additional sperm. According to
developing countries, the advisable method of monitoring is a Cochrane review, there is insufficient evidence to recommend
probably the regimen of one or two ultrasound examinations any specific preparation technique (Boomsma et al., 2007).
after CC stimulation combined with hCG injection, this
means prefect timing and avoidance of multiples by cancella- Addition of substances in sperm preparation
tion the cycle if three or more follicles of 14 mm or more are Whether the addition of substances such as pentoxyphylline,
found. The use of gonadotrophin-releasing hormone antagon- kallicreine, follicular fluid etc. may improve the results
ists to overcome the problem of unexpected premature LH remains unclear and certainly unproven. On the other hand, it
surges is effective but too expensive to be routinely used in is important to recognize that sperm preparation methods
developing countries. may induce damage to spermatozoa by increasing ROS gener-
ation by spermatozoa and by removing the scavengers from the
Factors affecting embryo implantation seminal plasma. More studies that investigate whether treating
Endometrial thickness/polyps spermatozoa with solutions containing antioxidants during
A trilaminar image rather and a greater endometrial thickness sperm preparation can improve PR with IUI in selected cases
provide a favourable prediction of pregnancy in IUI (Hock are needed. Two double-blind randomized studies evaluated
et al., 1997; Esmailzadeh and Faramarzi, 2007). Treatment the effect of PAF exposure on sperm during semen processing
should not be cancelled because of inadequate endometrial for IUI (Roudebush et al., 2004; Grigoriou et al., 2005). They
thickness (De Geyter et al., 2000). The use of ethinyl estradiol demonstrate a significantly higher PR for the PAF-treated
in clomiphene-stimulated cycles looks promising but requires group in a subpopulation of couples without male factor subfer-
confirmation (Gerli et al., 2000). If polyps are present, hystero- tility. Until now, there is no evidence that one specific sperm
scopic polypectomy before IUI is an effective measure to washing procedure is superior to the other methods in IUI
enhance pregnancy results (Pérez-Medina et al., 2005). programmes, but comparative studies are urgently needed.

Which catheter to use Fallopian sperm perfusion


In IUI programmes, most studies indicate that the catheter type In Fallopian tube sperm perfusion (FSP), a large volume of a
does not affect the outcome after (Lavie et al., 1997; Smith sperm suspension is inseminated intrauterine with excellent
et al., 2002; Fancsovits et al., 2005). On the other hand, results in cases of unexplained infertility (Kahn et al., 1992,
Proctor and Boone (2007) recently showed that although the 1993). A Cochrane review showed that FSP gives rise to
flexible catheter costs more than the rigid catheter, it is associ- higher PR in couples with unexplained subfertility (Cantineau
ated with a higher PR, which decreases costs of IUI treatment et al., 2004). Results suggested the possibility of differential
because fewer cycles are needed. effectiveness of FSP depending on catheter choice. For other
indications, FSP has not been proven more effective compared
The use of aspirin and luteal phase support with IUI.
There is no evidence so far that luteal support with progester-
one and/or hCG affects the conception rate in IUI programmes The effect of the abstinence period
with the exception of treatment regimen making use of GnRH Abstinence did not influence sperm morphology, total or grade
analogues. A motility, or sperm DNA fragmentation in a prospective study
Low-dose aspirin may improve uterine perfusion in women, described by De Jonge et al. (2004). A short (24 h) abstinence
but its value in assisted reproduction remains very controver- period negatively influenced chromatin quality. An abstinence
sial (Gelbaya et al., 2007; Khairy et al., 2007; Ruopp et al., interval of 3 days or less was associated with higher PR
2007). Therefore, it should not be routinely recommended in following IUI (Jurema et al., 2005).
assisted reproduction.
Immunologic male subfertility
Laboratory factors Most studies demonstrate a clear association between sperm
Sperm washing methods surface antibodies and the fertility potential of the male
Preparation and washing will remove reactive oxygen species (Adeghe, 1992; Acosta et al., 1994).
(ROS) and prostaglandines. The prostaglandines have to be In 1997, we published a prospective study comparing the
removed since they will cause severe uterine cramps when a effectiveness of the first-line IUI approach versus IVF for
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Ombelet et al.

male immunological subfertility (Ombelet et al., 1997b). The In this selected group of patients, it is unwise to start with
objective of this prospective study was to compare success assisted reproductive techniques such as IVF and ICSI since
rates after two different treatment protocols, COH –IUI these techniques are more invasive, more expensive and
versus IVF. Both IUI and IVF yielded unexpected high PR in more at risk for genetic disorders and obstetric complications.
this selected group of patients with long-standing subfertility Promoting IVF and ICSI to result in pregnancy ‘as quick as
due to sperm surface antibodies. Since cost– benefit analysis possible’ ignores the advantages of IUI completely.
comparing COH – IUI with IVF may favour a course of four
IUI cycles, we concluded that IUI can be used as the first-line
therapy in male immunological subfertility.
Although most fertility centres use IVF/ICSI in case of References
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(Abbasi et al., 1987). A Cochrane review, based on the results association with the genesis of reactive oxygen species by human
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Albano C, Nogueira D, Cortvrindt R, Smitz J, Devroey P. Avoidance of
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