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In the Management of Subfertile
Couples
Dr. JEHAD YOUSEF
FICS F!CO"
A#HAYA$ A!$ CE%$E!
AMMA% & JO!DA%
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Ob'e(ti)es of the *resentation

To examine the current indications, clinical and

laboratory methodologies used in IUI and the impact
of female

and male factors on success.

Emphasis is centered

in questioning the following:
- The alue of IUI against timed

intercourse.
- IUI application with or without !"#.
- Timing and frequency of
IUI.
- Impact of arious parameters on success.
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Artifi(ial Insemination +A.I.H,

Intra-aginal insemination $I%I&

Intra-cerical insemination $I!I&

Intrauterine insemination (IUI)

'allopian tube sperm perfusion $'()&

(perm Intra-fallopian insemination $(I'I&

*irect Intra-peritoneal insemination $*I)I&

Intra-follicular insemination $I'I&

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Intrauterine Insemination

The rationale is that

increasing the
density of both
eggs and sperm
near the site of
fertilization will
increase the
likelihood of
pregnancy.
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In-i(ations for IUI
+
The impossibility of
vaginal ejaculation
- psychogenic or organic
impotence
- severe hypospadias,
retrograde ejaculation
- cry preservation of sperm
in cases of cancer
treatment.
+
Abnormal male factor
- oligospermia
- asthenospermia
- teratospermia
+
Unexplained infertility
+
Cervical factor infertility
+
Husband is aay from ife for
long time (or! abroad)
+
HI" negative omen ith
processed semen of HI" #ve
husband$
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IUI . Step b/ Step

)atient,s selection

-atural cycle or

!ontrolled "arian stimulation.

.onitoring of treatment, to measure the growth of

follicles, indiiduali/e drug doses, and preent hyper
stimulation.

(perm preparation

Insemination

0uteal support.
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Sele(tion of patients

A "alid indication for IUI

%ormal or mildly abnormal semen parameters (Semen analysis

within months of the planned !"!#

%o evidence of intrauterine disease and patent tubes

(at least one) as shon in a $ecent %S& or (laparoscopy '
hysteroscopy#

&emale age ' () years *

(+ay ) &,H ' -./-0 mIU12l3 if age 4 )5 yrs)
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(rotocol of natural cycle !"!

.onitoring begins 12 days before expected menses

by T%( for follicular maturation.

"nce a mature si/ed follicle of 13-45 mm 6 7 8mm

trilaminar endometrium are obtained the woman will
monitor urinary 0# eery 5-9 hours.

Intrauterine insemination is timed :2-5; hours from

the 0# surge and will be repeated within 14 hours if
the oocyte had not released as yet.
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Controlle- o)arian h/perstimulation
before IUI
6 %umber of oocytes available
( chance of fertili7ation )
6 ,teroid production
( chance of implantation )
6 It may correct subtle ovulatory disorders3 such as
luteini7ed unruptured follicle syndrome3 not detected
ith routine diagnostic studies
6 2ore exact time to ovulation and insemination can be
determined

$he rationale
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-
2enses is the mar!er for onset of uterine1endometrial cycle$
-
inter/cycle &,H is the mar!er for functional onset of ovarian cycle$
-
8nly those antral follicles hich coincide ith the inter/cycle rise in
&,H can enter the final stages of follicular groth
o
v
u
l
a
t
i
o
n
o
v
u
l
a
t
i
o
n
In
terc
ycle

&
,
H

S/n(hroni0ation of the
menstrual (/(le
)rown *+,-
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S/n(hroni0ation of the
menstrual (/(le
Controlling the timing of occurrence of inter/cycle increase
in &,H 9

Timely use of :; (; mg estradiol valerate3 <8 =I+ starting

) days before the onset of menses of the previous cycle$

,hort/term use of the 8C pill for 5 to ;- days in the cycle

preceding stimulation cycle$
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Clomiphene citrate or similar drugs

u/h2> or highly purified u/h2>

<urified u/&,H or highly purified u/&,H

?ecombinant (r/&,H)

Combinations
----------------------------------------------------------------------

&n$% agonists in combination with h.& and'or /S% (long,

short or ultra short protocol#

&n$% antagonists in combination with h.& and'or /S%

(fi0ed or variable protocol#
O)arian Stimulation *roto(ols
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1hi(h o)arian stimulation to
(hose before intra2uterine
insemination3
1rug 2ost3 1rug availability and (atient acceptability

CC is an effective alternative for young omen ith good

prognosis3 hereas in the remaining cases h2> or &,H
ould be the preferable drug$

r&,H "s Urinary preparations 9 %o difference in clinical

pregnancy rate$

There is no advantage in routinely using >?h/a in

conjunction ith gonadotrophins for ovulation stimulation
At the moment one should use the least expensive
medication$
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Monitoring o)arian stimulation
Transvaginal ultrasound scanning :
. No. & size of follicles
. Pattern & thickness of endometrium
Estrogen blood level
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En-ometrial thi(4ness 5 Monitoring
o)arian stimulation
0
500
000
500
!000
!500
"000
"500
0 5 0 5 !0
Endometrium (mm)
E2
(pmol/L)
After @eev ,hoham
n = 183
Correlation beteen :; and endometrial thic!ness
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Optimum o)arian stimulation
For IUI

; / ( follicules ith A -B C -D mm$

:stradiol blood level 9

-0./;0. pgm 1 ml per -0 mm follicle$

:ndometrium D mm thic! E trilaminar$

!"! between 2ycle 1* and 1*4.

Cancellation 9

F follicles -0 mm irrespective of :; level

:stradiol -0.. pg1ml$

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Sperm pro(essing
!ationale

Concentration of progressively motile and morphologically

normal spermato7oa into a small volume of culture fluid$

:lemination of seminal <>3 lympho!ines3 cyto!ines and

infectious agents

?educe the number of free oxygen radicals$

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Sperm pro(essing

,imple ,perm ash

,im/up folloing sperm ash

once or tice$

+ensity gradient column

separation (filtration in <ercoll
gradients3 <ure,perm or Isolate)$

Adding chemicals to the ashed

sperms (caffeine 3 pentoxyfylline3
;/deoxyadenosine3 !alli!rien3
bicarbonate3 platelet activating
factor) **
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Sperm pro(essing

,amples ith an acceptable number of motile sperm ( 4 ;.

millions 1 ml ) can be processed efficiently by sperm ash
tice and sim/up$

<oor Guality semen samples should be processed using

density gradient centrifugation +>C$
2orshedi 2 et al3 ;..)
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$iming an- Fre6uen(/ of IUI
#i$ed %rotocol:
& 'ingle insemination:
"( ) *0 hrs %ost ) h+,
& double insemination:
-ithin ! & *. hrs %ost - h+,

/ariable %rotocol:
& T/' "( h %ost h+,:- 0vulated single 121
- Not 0vulated 121 at once
121 !* hrs later
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IUI te(hni(al aspe(ts
- (artially filled urinary bladder3 lithotomy position 5 abdominal "S
- &ently and atrumatically clean the cervi0 with saline soaked swab
introduce !"! catheter through cervi03 no touch to fundus
- Slowly inject 6.-.67 ml of processed semen
- Slowly withdraw catheter
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Management follo7ing IUI

=ed rest
A -. minutes bed rest after IUI has a positive effect
on <?$

Intercourse ithin -;/-B hours of IUI$

Huteal phase support3 8(T!89S:

/ hC>9 -$0.. IU hC> ) E F days after -
st
hC>
/ +uphastone -. mg <8 1 B hourly after IUI x -( days
/ Cyclogest (.. mg supp$ <" or <?I once daily after IUI x
-( days
/ Utrogestan9 -.. mg <" 1 B hourly after IUI x -( days
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E)i-en(e base- re(ommen-ations for
pra(ti(ing IUI
Grade A recommendations*

!ouples with mild male factor fertility problems,

unexplained fertility problems or minimal to mild
endometriosis should be offered up to six cycles of
intra-uterine insemination because this increases the
chance of pregnancy.
9!2; >uidance &eb$ ;..(
< &rade = : based on randomised controlled trials
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E)i-en(e base- re(ommen-ations for
pra(ti(ing IUI
Grade A recommendations

<here intra-uterine insemination is used to manage

male factor fertility problems, oarian stimulation
should not be offered because it is no more clinically
effectie than unstimulated intra-uterine insemination
and it carries a ris= of multiple pregnancy.
9!2; >uidance &eb$ ;..(
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E)i-en(e base- re(ommen-ations for
pra(ti(ing IUI
Grade A recommendations

<here intra-uterine insemination is used to manage

unexplained fertility problems, both stimulated and
unstimulated intra-uterine insemination are more
effectie than no treatment. #oweer, oarian
stimulation should not be offered, een though it is
associated with higher pregnancy rates than
unstimulated intra-uterine insemination, because it
carries a ris= of multiple pregnancy.
9!2; >uidance &eb$ ;..(
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E)i-en(e base- re(ommen-ations for
pra(ti(ing IUI
Grade A recommendations

<here intra-uterine insemination is used to manage

minimal or mild endometriosis, couples should be
informed that oarian stimulation increases pregnancy
rates compared with no treatment, but that the
effectieness of unstimulated intra-uterine
insemination is uncertain.
9!2; >uidance &eb$ ;..(
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E)i-en(e base- re(ommen-ations for
pra(ti(ing IUI
Grade A recommendations

<here intra-uterine insemination is underta=en, single

rather than double insemination should be offered.

<here intra-uterine insemination is used to manage

unexplained fertility problems, fallopian sperm
perfusion for insemination $a large-olume solution, 5
ml& should be offered because it improes pregnancy
rates compared with standard insemination
techniques.
9!2; >uidance &eb$ ;..(
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%umber of trials of IUI 3

<regnancies resulting from IUI occur during early

treatment cycles$
:ighty/eight percent of pregnancies occur in the first three
cycles of IUI and D0$0J ithin the first four cycles
(2orshedi 2 et al3 ;..))$
2ontinued !"! beyond four trials
is not recommended
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.easures to improve results

Use of Aspirin in IUI Cycles Hsieh KK et al3 ;... ?CT9

Higher pregnancy rate and better endometrial pattern
ere achieved in patients ith thin endometrium after aspirin
administration$

Type of catheter ,mith et al3 ;..;3 ?CT 9

%o difference in <? hen using softer Lallace catheter or the less
pliable Tomcat catheter

"aginal misoprostol at the time IUI =ron et al$ ;..- ?CT 9

;.. / (.. Mg of misoprostol vaginal insertion at the time
of insemination is associated ith higher <?$
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.easures to minimize risk of
8%SS

,halev :3 et al3 -DD0 ?CT 9

s$c$ injection of .$- mg >n?Ha
(decapeptyl) instead of hC> in IUI treatment cycles at
high ris! of 8H,,$

+e >eyter3 et al -DDF ?CT 9

Transvaginal aspiration of
supernumerary follicles (more than three follicles si7ed
4 -( mm) does not reduce the <?s and reduce multiple
pregnancy rate$
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1hat is the upper age limit
for IUI 3

2ost studies have suggested that it is an effective

treatment option for omen under the age of (. yrs
,uccess of intrauterine insemination3
in omen aged (./(; years3 Habe3 et al3
&ertility and ,terility3 "ol 5B3 %o -3 Nuly ;..;
These researchers found in their revie that it may be
a reasonable approach for omen under the age of ()$
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1here IUI shoul- be -one3

Although IUI can be performed in an optimi7ed office

but <atients need to run from gynecologist to the lab$
&ragmented care because of poor coordination$

Ideally in an optimi7ed clinic in cooperation ith an I"&

unit
/ I"& choice E &ree7ing any extra embryos in case of
over/response
/ * ,elective follicular reduction in case of over/
response

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SUMMA!Y

IUI is relatively simple3 non/invasive3 cheap E easily

repeatable$

Careful selection of patient is important$

There is good evidence in the literature in favor of IUI as a

cost/effective treatment for unexplained and mild3 moderate
male factor sub fertility$

Although it may ta!e relatively more treatment cycles to

achieve pregnancy3 there are considerable advantages to the
patient in terms of ris! 1 benefit ratio and financial cost as
compared ith other A?Ts$

&ailure of ( / F trials of >n$ stimulated IUI in unexplained or

mild male infertility3 is an indication for I"&$
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1r. >.?ousef /!2S,/$28&
e/mail 9 ramoammanOyahoo$co$u!