Intra uterine insemination for unexplained infertility
for Unexplained Infertility
Presented byPresented by
Ahmed Walid Anwar Morad, M.DAhmed Walid Anwar Morad, M.D
Assistant Professor of Obstetrics and GynecologyAssistant Professor of Obstetrics and Gynecology
Banha Faculty of MedicineBanha Faculty of Medicine
The main objective of this
presentation is to spotlight on the
role of IUI in the treatment of
Unexplained infertility means that ,couple does
not conceived after 1 year of unprotected
vaginal sexual intercourse, with basic infertility
evaluation shows no obvious abnormality
(RCOG guidelines,1998; Randolph,2000; ASRM,2006).
15% to 30% of infertile couples
Basic investigations for diagnosis
of Unexplained infertility
Normal basic semen analysis according to
WHO criteria (WHO ,2010).
Patent fallopian tube confirmed by HSG.
Ovulation confirmed by mid-luteal serum
In unexplained infertility: the cause is not
defined ,so the treatment is empirical (ASRM, 2006).
Oral stimulating agents (CC /Oral stimulating agents (CC /
Gonadotropin injections with orGonadotropin injections with or
Bromocriptine, Danazol, Tubal
○ Availability of resources ,
○ Patients’ age ,
○ Duration of infertility.
The standard protocol is to:
○ Progress from simple to complex treatment options,
○ Balance the effectiveness against the cost and side effects.
(Ray et al,2012)
Suggested Protocol for Management of
Unexplained Infertility (Ray et al, 2012)
The role of IUI in treatment
of unexplained infertility
Other indications of IUI
Indications of IUI in unexplained infertility
Effectiveness of IUI in unexplained infertility
IUI involves the placement of
processed semen into the
uterine cavity around the time
of ovulation (Allahbadia and Merchant,2012).
increase the rate of
increasing the chance
that maximum number
of healthy sperms
reaches the site of
1. Ejaculatory failure: ( sever hypospadius ;retrograde
2. Male factor infertility (mild ;moderate)
3. Sperm cryopreservation prior to treatment of
4. Processed semen of HIV + husband for HIV
negative women (NICE, 2013)
Advantages of IUI
• Non invasive (like Pap smear).
• Bypass possible cervical mucous
• Easy: performance and training
• Minimal: cost and risk
Of the procedure
anger, loss of self esteem)
ESHRE Capri Workshop Group (2009)
IUI or stimulated ovary/IUI is indicated as
empiric treatment for all categories of
20% of couples after initial work-up.
Couples with mild male subfertility (20–40%)
50% of those in whom conventional
treatments have failed.
NICE Guidance Feb, 2013
In the treatment of unexplained infertility
The evidence does not support the use of IUI as
an alternative to expectant management .
IUI (with or without stimulation) should not be
routinely offered (exceptions e.g. when people
have social, cultural or religious objections to IVF)
Effectiveness of IUI in treatment of
(Guzick et al. 1998.)
Conclusions (Cochrane, 2012 )
: In stimulated cycles PR was higher with IUI compared to timed
Treatment % preg
Expectant (No treatment ) 1.3%
Natural cycle IUI 3.8%
Clomiphene+ IUI 8.3%
Gonadotropins+ IUI 17.1%
Unexplained Infertility :
PR with different treatment Options
NICE Guidance Feb, 2004 ; For unexplained infertility
ovarian stimulation should not be offered, even though
it is associated with higher pregnancy rates than
unstimulated IUI, because it carries a risk of multiple
Cochrane, 2012 ; risks and alternative treatment options
of stimulated IUI should be discussed.
NICE Guidance Feb, 2013 ; Do not offer oral ovarian
stimulation agents (such as clomifene citrate,
anastrozole or letrozole) to women with unexplained
IUI versus alternative insemination techniques
1 } Fallopian Tube Sperm Perfusion (FSP) :
Past : FSP is superior to IUI (Trout & Kemmann,1999) .
Later: a meta-analysis reported no clear benefit (Cantineau et
2} No difference between IUI and Intraperitoneal
insemination (IPI) (Noci et al,2007)
3} Intrauterine tuboperitoneal insemination (IUTPI) is
superior to IUI &FSP (CPR/cycle 29.4% ) (Mamas, 2006)
4} IUI is superior to Intracervical insemination ICI
(Besselink et al,2008).
IUI Vs. IVF for unexplained infertility
Starting treatment with IUI rather than IVF was
either cheaper or more cost-effective than IVF in
unexplained infertility (Goverde et al., 2000).
Cochrane, 2012 (Pandian et al, 2012)
IVF may be more effective than IUI+SO.
Due to lack of data from RCTs the effectiveness of
IVF for unexplained infertility relative to
expectant management, clomiphene citrate and IUI
alone remains unproven.
For people with:
○ unexplained infertility,
○ mild endometriosis or
○ mild male factor infertility,
who are having regular unprotected sexual intercourse:
advise them to try to conceive for a total of 2
years before IVF will be considered .
NICE Guidance Feb, 2013
IUI in stimulated cycles may
be considered while
waiting for IVF or when in
women with patent tubes,
IVF is not affordable
(ESHRE Capri Workshop Group, 2009)
Favorable Predictors of IUI
Factors related to couples
Factors related to therapy
1.Female age ≤ 35y (Morshedi et al, 2003 )
2.Shorter duration of infertility .
3. Type of infertility (Guven et al,2008)
Type of infertility Pregnancy rate
Primary inf. 7.9%
Secondary inf. 21.4
4. First treatment cycles (≤ 4).
Pregnancies resulting from IUI occur during the first 3-4
treatment cycles (88-95.5%; respectively)
(Morshedi et al,2003).
Aboulghar et al, 2001, suggested a maximum of 3
COH/IUI cycles for treatment of unexplained infertility
However ,others recommended up to 6 cycles
(Dickey et al, 2002; Morshedi et al,2003; Ray et al, 2012).
5. Cause of infertility: (Bourn Hall clinic, 1999
;Tay et al,2007; Wang et al,2008).
Higher PR with :
○ Unexplained infertility (9.2% to 22% )
○ Ovulatory dysfunction (19.2%)
Modest PR → Cervical factor (16.4%)
○ Endometriosis (11.9%)
○ Immunological infertility (10% )
♂ factor → the best PR with ejaculatory disorders (13.3%)
B. Therapy: (Allahbadia and Merchant,2012).
1.Use of CC/HMG-FSH compared with CC only.
-AFC > 5 (Ombelet et al, 2003)
-Preovulatory follicles : 2–3 follicles≥ 16 mm with
uniformly high-grade vascularity and E2 levels >500
pg/mL on the day of hCG administration. (Steures et al, 2004;
Bhal et al ,2001).
.3.Sperm parameters: generally
• Processed total motile sperm count ≥ 10 million, 24 h
survival > 70%, and normal sperm morphology of >4%
(according to Kruger’s criteria) predict pregnancy
outcome with 94% sensitivity, 86% specificity (Guven et al,
2008;Abdelkader & Yeh ,2009).(12.3 vs 2.8%)
• Initial sperm count, motility ?
4.Time of insemination,
preferably between D13 &16.
adequate thickness with trilaminar pattern
)Tomlinson et al ,1996(
Measures does not affect IUI
1. US monitoring & HCG induction of ovulation
versus urinary LH monitoring of ovulation.
HCG allow final follicular maturation (Kosmas et al, 2007)
2. GnRH agonist and antagonist. ↑complications
(Allahbadia and Merchant,2012).
3. Double IUI versus single IUI (Polyzos et al,2009).
4. Type of catheter: no significant difference in PR
when using the softer Wallace catheter or the less
pliable Tomcat catheter during IUI, with the standard
gentle non touch technique (Smith et al ,2002).
However , Merviel et al ,2010 recommended soft
5 . Luteal phase support do not appear major
requirements in IUI cycles (ESHRE ,2009)
6. Sperm preparation technique (ESHRE,2009).
How to improve IUI results?
Measures to↑ PR:
1. COH: all except sever male factor ( Risks???)
2. Vaginal misoprostol.????
(Brown et al,2001; Barroso et al,2001).
3. 10 -15minutes bed rest after IUI
(Saleh et al,2000 ; Custers et al, 2009 )
4. Cervical mucous aspiration before IUI
(Paasch et al, 2007)
5. Timed intercourse within 12 -18 h period: useful in IUI with low
number of motile sperm inseminated (Huang et al, 1998).
6. Postponing IUI until the observation of follicle rupture by TV
sonography ( PR;25% vs 8.8%) (Kucuk ,2008).
7. US guidance in IUI
(Ramón et al,2009; Oztekin et al,2013)
8. Pre-insemination hydrotubation
(Edelstam et al, 2008; Aboulghar et al, 2010 ; Morad & Abdelhamid , 2012)
1.Treatment of unexplained infertility is
empiric as no obvious abnormality was
2.Treatment of unexplained infertility is
very much dependent on availability of
resources and patients’ age and duration
of infertility .
3.OH with IUI is a simple ,cost-effective,
least invasive first-line treatment for
4.Couples should be fully informed about
the risks of IUI and COH as well as
alternative treatment options.
5. In unexplained infertility OH with IUI may be
considered while waiting for IVF or when
IVF is not affordable.
6. The pregnancy rates of FSP & Standard IUI
7.Pre-insemination hydrotubation, US guided
IUI , cervical mucous aspiration, post-
insemination bed rest for 10 min and vaginal
misopristol may improve IUI outcome .
8. In unexplained infertility, up to 6 cycles of
IUI should be considered before shifting to