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Role of
intrauterine
insemination in treatment of
infertility
Prof. Aboubakr
Elnashar
Benha university Hospital,
EgyptABOUBAKR ELNASHAR
CONTENTS
1. Definition
2. Rationale
3. Advantages
4. Indications
5. Contraindications
6. Complications
7. Evidence
8. Effectiveness
1. Factors affecting success
2. NNT
3. Cost effectiveness
Conclusion
ABOUBAKR ELNASHAR
Direct transfer of
processed semen into the uterine cavity
about the time of ovulation
1. DEFINE
ABOUBAKR ELNASHAR
2. RATIONALE
A. Direct transfer:
1. Bypass 3 of the natural barriers
1. Vagina
2. cervical mucus, and
3. cervix
that sperm have to traverse
B. Processed semen:
1. Washing:
1. organisms,
2. prostaglandins&
3. antibodies
2. Deposition of a bolus of
concentrated,
motile,
morphologically normal sperm
2. More sperm are
placed
closer to the site of
fertilization
(fertilization occurs in
the fallopian tube).
ABOUBAKR ELNASHAR
3. ADVANTAGES
1. Non invasive (like Pap smear).
2. Inexpensive.
3. Easy to perform
4. Training is easy
5. Risks are minimal
6. Antenatal & perinatal complications:
like pregnancies from normal S I
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4. INDICATIONS
A.Male:
I. Ejaculatory failure:Retrograde ejaculationHypospadiusImpotenceInfrequent Intercourse during fertile period.
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Semen analysis: WHO, 2010
:
:Lower reference limitParameter
1.5 ml Volume
7.2 pH
15 million/ml Concentration
39 million/ejaculate Total sperm number
40% or PR: 32%
Total motility: (PR+NP)
58% live spermatozoaVitality
4% (strict criteria).Normal forms
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II. Male infertility: Mild
Severe male infertility:
Count<5million/ml (15million/ml)
Normal morphology <2.5% (4%)or
Total Motility <10% (40%)
Not candidate for IUI but ICSI.
ICSI is more cost effective than IUI
(Van Voorhis et al,2001)
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Before processing:
1. Total Count:
PR are lower if the semen sample contains,
10 million sperm in total (40 million)(Van Voorhis et al., 2001).
2. Total sperm motility
30% before sperm preparation (40%)
(Ombelet et al 1996; Dickey et al 1999, Montanaro et al 2001, Lee et al,
2002)
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3. TMSC/ejaculate
> 5 million/ejaculate are indicated for treatment with
IUI.
can be used as the method of choice for diagnosis
and treatment of male infertility(Hajder et al, 2016)
In the absence of teratospermia
TMSC does not appear to impact PR in subfertile
couples undergoing IUI.(Hassan et al, 2017)
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After processing:
Insemination motile count (IMC) and
Sperm morphology
(Ombelet et al 2003, 2008; Duran et al , 2002. SR; Butcher et al, 2016)
Most valuable parameters to predict IUI outcome
There is a trend towards increasing conception
rates with increasing IMC
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Infertility work -up
No tubal factor
Washing procedure
IMC> 1 million
IMC< 1 million
Morphology >5%IMC< 1 million
Morphology <5%
IVF
< 30 % or no fertilization
ICSI
IUI 4x
(Ombelet et al 2008. ESHRE Monograph)
B. Female:
I. Cervical factor:
cervical mucous hostility, poor cervical mucous
significant improvement of conception for IUI compared
with TI
(Cohlen;2005, MA of RCT)
II. Endometriosis:
mild & moderate
IUI with OS, instead of EM: increases LBR(Tummon et al., 1997; ESHRE, 2009)
IUI with OS within 6 months after surgical tt,
PR are similar to those achieved in un infertility (Werbrouck et al., 2006; ESHRE, 2009)
III. Vaginismus
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C. Both:
I. Immunological:
Male antisperm antibodies
Female antisperm antibodies (cervical, serum)
II. Unexplained infertilitybasic investigations are normal
(Hajder et al, 2016)
III. While waiting for IVF
IV. Women with patent tubes and IVF is not
affordable.
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5. CONTRAINDICATIONS1. Cervical atresia
2. Cervicitis
3. Endometritis
4. Bilateral tubal obstruction
5. Most cases of amenorrhea
6. Severe oligospermia.
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6. COMPLICATIONS
1. Uterine contraction
2. Intrauterine infection
PID: rare
0.01-0.2%
3. Psychological:
Guilt, anger, loss of self esteem
Relatively low success rate /cycle.
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4. Complications of COS:
Multiple pregnancy.
increased with
age < 30
6 mature follicles
E2 > 1000 pg/ml
Gnt.
risk is much lower with CC.
MP (7-13%) (Ombelet et al 2006).
OHSS
Only observed in
Gnt cycles following administration of hCG
Rarely occurs in women treated with CC
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7. EVIDENCE
I. IUI for unexplained or male infertility
1. NICE, 2013
No IUI
Advise them to try to conceive for a total of 2y
(including up to 1y before their fertility investigations)
IVF will be considered.
Exceptions: Social, Cultural, Religious
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Criticism against NICE recommendations:
Evidence on which the recommendation was made
was low to very low quality
Survey:
<4% of fertility clinics in the UK discontinuing
IUI
(Kim et al., 2015; Nandi et al., 2015).
Many gynecologists continuing to offer IUI,
instead of IVF, as first-line treatment
IVF:
was not regarded as an established first-
line option for unexplained infertility
compared to IUI
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2. Bensdorp et al.2015
multicentre RCT
17 fertility clinics in the Netherlands.
Group I:
3 cycles of IVF with SET. (n=201)
(plus surplus cryo embryos)
Group II: (n=194)
6 cycles of IVF in a modified natural cycle.
Group III:
6 cycles of IUI with OS (n=207)
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All three methods:
comparable proportions of healthy singletons around 50%
comparable proportions of multiple pregnancies 6% (IVF-SET)
5% (IVF MNC), and
7% (IUI-OS).
No reason to abandon IUI with OS as a first line
treatment for couples with unexplained or mild male
infertility.
It is cheaper, less invasive and has no higher MPR
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3. Tjon-Kon-Fat et al, 2015
IUI: significantly less expensive
No significant difference
No evidence in support IVF as a first line between
18 and 38 y
IUI OS
should remain the treatment of first choice for
unexplained or mild male infertility
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II. IUI for unexplained infertility
1. AMIGOS Trial Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation
(National Institute of Child Health and Human Development (NICHD)New Eng.
J. of Med 2015)
– 12 clinical sited in USA.
– 900 couples with un infertility.
– Age 18-40 years old.
– Up to 4 OS cycles with IUI
LBR Cong. Anomalies
Letrozole 18.71% 3.6%
Gonadotropin 32.2% 3.1%
Clomiphene 23% 4.3%
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2. IUI Vs TI for unexplained infertility.(Veltman-Verhulst et al, 2016, Cochrane SR).
IUI Vs TI or EM both in natural cycle
no evidence of a difference in cumulative LBR
LBR
TI:16%
IUI: 15% to 34%.
IUI Vs TI or EM both in stimulated cycle
No evidence of a difference in LBR
LBR
TI: 26%
IUI: 23% to 50%.
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No conclusive evidence of a difference in
LBR or
multiple pregnancy
in most of the comparisons for couples with
unexplained infertility treated with IUI when
compared with TI, both with and without OS.
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3. IUI Vs IVF for unexplained infertility(TjonKonFat et al, 2016)
similar LBR
insufficient evidence to conclude that IUI or IVF is effective
compared to TI in un infertility.
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4. IUI Vs IVF for unexplained infertility.
Couples were randomized to receive either
3 cycles of IUI+ OS or
1 cycle of IVF (Nandi et al, 2017)
Singleton LBR:
not significantly different (24.7% vs 31.1%) with an absolute risk difference of 6.4% (95% CI
5.8% to 18.6%).
Multiple pregnancies per live birth:
No significant difference (13.8% vs 8.3%)
(relative risk, 0.6; 95% CI 0.142.4).
OHSS:
IUI: no cases
IVF: 3 cases of OHSS (3.7%)ABOUBAKR ELNASHAR
8. EFFECTIVENESS1. Factors affecting success
CPR per cycle.
1. Female and male age
2. Male smoking
3. Female BMI
4. Infertility status: primary/secondary infertility
5. Inseminating motile count (IMC)
6. Ovarian stimulation(Thijssen et al, 2017)
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Treatment PR/cycle NNT 95% CI Source
IUI 5 32 (12.-46) Guzick et al. (1999), Martinez
et al. (1990) Steures et al.
(2007)
CC/IUI 7 14 (7.-100) Deaton et al. (1990)
FSH/IUI 12 11 (9.16) Guzick et al. (1999)
IVF 31 4 (3.7) Hughes et al. (2004)
2. PR per cycle and NNT per cycle
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3. Cost Effectiveness
initially treatment with IUI
more cost-effective than IVF in most cases of
Unexplained
Mild male infertility.
(Carceau et al 2002; Ombelet et al 2005)
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CONCLUSION
IUI
least expensive
least invasive
least stressful
least hazardous.
IMC> 1 million is a good candidate for IUI
In unexplained or mild male infertility
No evidence in support of IVF as a first line
IUI OS should remain the treatment of first choice.
ABOUBAKR ELNASHAR
You can get this lecture from:1.My scientific page on Face book:
Aboubakr Elnashar Lectures.
https://www.facebook.com/groups/2277
44884091351/
2.Slide share web site
3.elnashar53@hotmail.com
4.My clinic: Elthwara St. Mansura
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