Direct transfer of
processed semen into the uterine cavity
about the time of ovulation
1. DEFINE
ABOUBAKR ELNASHAR
2. RATIONALE
A. Direct transfer:
1. 3 of the natural barriers (vagina, cervical mucus,
and cervix) that sperm have to traverse are
bypassed.
2. More sperm are placed closer to the site of
fertilization (fertilization occurs in the fallopian
tube).
B. Processed semen:
1. Washing organisms, prostaglandins& antibodies
2. Deposition of a bolus of concentrated, motile,
morphologically normal spermABOUBAKR ELNASHAR
ADVANTAGES OF IUI
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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3. INDICATIONS
A.Male:
I. Ejaculatory failure:Retrograde ejaculationHypospadiusImpotenceInfrequent Intercourse during fertile period.
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II. Male subfertility: Mild
Severe male infertility:
Count<5million/ml (15million/ml)
Normal morphology <2% (4%)or
Motility <10% (40%)
Not candidate for IUI but ICSI.
According to the WHO criteria, the diagnosis of mild
male infertility problem is made when two or more
semen analysis results show one or more variables
below the fifth centile.
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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
lower limit
3 million motile sperm
(Strandell et al., 2003),
ABOUBAKR ELNASHAR
Infertility work -up
No tubal factor
Washing procedure
IMC> 1 million
IMC< 1 million
Morphology >2IMC< 1 million
Morphology <2%
IVF
< 30 % or no fertilization
ICSI
IUI 4x
(Modified from Ombelet et al 2008. ESHRE Monograph) ABOUBAKR ELNASHAR
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 32%
Total motility: (PR+NP)
PR (a+b)
58% live spermatozoa Vitality
4% (strict criteria).Normal formsABOUBAKR ELNASHAR
Abnormal semen
ICSI
TT of varicocele if palpable
Hormonal tt if low FSH &Testost.
Treatment of infection ?
Mild:≥2 NM, ≥5M, ≥10%TM Severe or
Azoospermia
3 trial IUI
ABOUBAKR ELNASHAR
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 infertilityspermiogram is normal with normal female factor.
(Hajder et al, 2016)
III. While waiting for IVF
IV. women with patent tubes and IVF is not
affordable.
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4. CONTRAINDICATIONS1. Cervical atresia
2. Cervicitis
3. Endometritis
4. Bilateral tubal obstruction
5. Most cases of amenorrhea
6. Severe oligospermia.
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5. STEPSI. SELECTION & COUNSELING
II. OVARIAN STIMULATION
III. MONITORING OF
FOLLICULAR GROWTH &
ENDOMETRIAL DEVELOPMENT
IV. TIMING OF INSEMINATION
V. SPERM PREPARATION
VI. INSEMINATION
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I. SELECTION1. Basic investigations of infertility:
Semen analysis
Midluteal progestrone
HSG
2. Baseline ultrasound
3. Ovarian reserve Tests
Indications.
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COUNSELING Confidence of husband.
Cost
Complications.
Steps
Success rate: 15–20 % / cycle
Couple question & answer information:
increase effectiveness & promote +ve self
approach.
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II. OVARIAN STIMULATION
Rationale:
1. To increase the number of oocyte available
(< 4 mature follicles) for insemination & thus the
chance of implantation
2. To increase steroid production which may improve
the chance of fertilization & embryo implantation.
Disadvantages:
1. OHSS
2. Multiple pregnancy
3. Cost of drugs & monitoring. ABOUBAKR ELNASHAR
III. MONITORING:
1. Follicular growth &
2. Endometrial development
Baseline U/S:
AFC
To exclude ovarian cysts
D3 FSH & LH:
Elevated LH & FSH: poor follicular response.
Raised LH/FSH: PCOS: excessive response.
From D8 of stimulation: serial U/SABOUBAKR ELNASHAR
IV. TIMING OF INSEMINATION
1. US
2. Urine LH surge
Rationale:
• Viable spermatozoa should be present in the female genital system at the time of ovulation.
• Sperms retain their fertilizing capacity for 40-80 h
• oocyte have life span of 12-24 h after ovulation.
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Methods for timing of ovulation:
1. Urinary LH surge:
Serum LH surge (+12 h)
Urine LH surge (serum LH peak) (+24 h)
Follicular rupture
IUI 36 h after positive urine test .
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2. U/S folliculometry:
• The exogenous HCG mimics the endogenous LH surge &offers the advantages that the onset of LH surge is knownprecisely.
• HCG is given when the leading follicle is 17-20 mm.
• HCG should be withheld if
1. The number of mature follicles > 4 or
2. Number of follicles > 12 mm > 8
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No evidence of a difference in LBR between
hCG injection vs LH surge
urinary hCG vs rec hCG or
hCG vs GnRHa
Optimum time interval from hCG injection to IUI:
24 h to 48 h.
No difference in LBR
Choice should be based on
1. hospital facilities,
2. convenience for the patient, medical staff,
3. costs and dropout levels[Cochrane SR , 2014].
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Number of inseminations:
• One insemination performed
34-38 h after HCG or
24-36 h after urine LH surge
• The next day after HCG
(Egyptian fertility center)
• 2 inseminations performed:
24 & 48 h after HCG.
12 & 34 h after HCG
(Rangi et al,1999).
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V. SPERM PREPARATION1. Swim up method
2. Density gradient centrifugation.’ (DGC)
Collection of semen:
1. Sperm is obtained by masturbation into a sterile container
after 3-5 days of sexual abstinence.
2. Avoidance of lubricantsmost are toxic to sperm.
If a lubricant is needed, instruct the client to prevent contact
between the lubricant and glans.
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Selection of the method:
1. Normozoospermia:
Swim up
simple & quick way of producing a purified inseminate
containing a high percentage of progressively motile
spermatozoa.
2. Sperm disorders: (OAT):
DGC: superior to swim up technique.
3. High leukocyte concentration (>1x107/ml):
Swim up from semen,
DGC (sperm wash only after cell separation)
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VI. INSEMINATION
Equipment
Speculum
1 cc sterile syringe with blunt cannula
Disposable polyethylene insemination catheter
Two types of catheters
1. Relatively rigid single sheath catheters
(straight or with a preformed curve) that
cannot be bent
2. Double sheath catheters with an external
flexible sheath that will maintain a curve and
a very soft internal catheter.
PR and LBR:
same for flexible and rigid catheters
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Selection of catheter:
1. Soft flexible catheter can be formed to accommodate the curve of the
patient's uterus
less traumatic to the endometrium.
patients barely feel the IUI procedure
2. An internal wire or rigid stylet
may be used with the external sheath for difficult
IUIs.
3. Stiffer catheters easier to insert into the uterine cavity
do not bend
more
uncomfortable for the patient
traumatic to the endometrium
vaginal bleedingABOUBAKR ELNASHAR
ABOUBAKR ELNASHAR
Precautions:
1. Aseptic technique to avoid infection
Povidone iodine should not be used to cleanse the
cervix toxic to sperm
Antibiotic prophylaxis is unnecessary.
2. Gentle technique to avoid trauma of the
endometrium:
cramping & bleeding:
adversely affect the survival of spermatozoa
ABOUBAKR ELNASHAR
Standard technique:
1. Ask women with AVF uterus to maintain a full
bladder
facilitate straightening of the uterus.
not useful for women with RVF uteri.
2. Lithotomy position
3. The cervix is exposed with bivalve speculum &
rinsed with saline
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4. The catheter is firmly connected to the cone of 1cc
tuberculin syringe
Plunger is withdrawn slightly& the sperm
suspension is then aspirated from the test tube
into the catheter without any air bubbles
Sperm is suspended in a small volume of media,
no more than 0.5 mL
prevent expulsion or reflux from the cervix and
uterine contractions after it is inseminated into
uterus.
ABOUBAKR ELNASHAR
5. The catheter tip is advanced to a depth of
approximately 6 to 6.5 cm.
Try not to let the catheter touch the fundus
cramping and, in some cases, disruption of the
endometrium and bleeding: toxic to embryo
development.
ABOUBAKR ELNASHAR
6. If difficulty is encountered with insertion of the catheter
use of a rigid stylet
abdominal US guidance
avoid use of a tenaculumuterine contractions and patient discomfort.
If catheter passage through the cervix is difficult:
grasp the cervix with tenaculum to straighten the
utero-cervical angle by gentle traction
ABOUBAKR ELNASHAR
7. Inject the sperm
Leave the catheter in place for short time
withdraw it slowly avoid suction effect & prevent reflux.
Sperm are present in the fallopian tubes as early as 5
min after insemination
8. Patients rest in
supine or
reverse Trendelenburg position for 10 min
higher PR in rested patients compared with those
who were immediately mobile post IUI
(PR 25% vs 10%).
ABOUBAKR ELNASHAR
Postprocedure care
The patient may resume her normal activities after
insemination.
Increased wetness after the procedure
Loosened and watery cervical mucus
does not mean the sperm specimen has flowed
out
patients should be reassured about this.
Abdominal cramping or discomfort may;
acetaminophen
Light bleeding or spotting
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Intercourse
within 12-18 h If they wish to do so
Pelvic discomfort
ovarian enlargement from CC or Gnt:
No intercourse.
A urinary or serum pregnancy test
2 w after IUI.
If the patient has received hCG for ovulatorytriggering, it is important to inform the patient that a urinary or serum pregnancy test may remain positive up to 12 days after the injection.
ABOUBAKR ELNASHAR
LPS:
Vaginal progesterone
after ovulation induction/IUI:
higher LBR with compared with no
progesterone support (SR of RCT)
Benefit was restricted to
Gnt stimulated cycles.
history of unexplained RPL
luteal phase <10 days.
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Oral dydrogestrone
effective as vaginal progesterone for LPS
mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group.(Khosravi et al, 2015)
No difference
in PR and LBR per cycle and per patient
according to the use of LPS in IUI cycles using
gonadotropins.(Aytac et al, 2016)
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6. COMPLICATIONS
1. Uterine contraction
2. Intrauterine infection
Upper genital tract infection is a rare
PID: 0.01-0.2%
3. Psychological:
guilt, anger, loss of self esteem
Relatively low success rate / cycle.
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4. Complications of COH:
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 exogenous Gnt cycles following
administration of hCG or after GnRHa
rarely occurs in women treated with CC
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7. FACTORS AFFECTING SUCCESS
1. Female and male age
2. Male smoking
3. Female BMI
4. Ovarian stimulation
5. Inseminating motile count (IMC)
6. Infertility status(i.e. primary/secondary infertility). (Thijssen et al, 2017)
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
4.My clinic: Elthwara St. Mansura
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Endometrial scratching injury ESI
significantly improves the outcome of IUI in women
with un infertility especially when conducted 1 month
prior to IUI(Maged et al, 2016)
Piroxicam (Feldene)
10 mg/d on days 4-6 after IUI
increased PR
No effect on abortion, multiple pregnancy, (Zarei et al, 2016)
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B. Technique:
1. Stimulation
Natural cycle vs stimulated
Up to 5 mature follicles
Use of CC/HMG-FSH compared with CC for OS
2. Sperm preparation
Sperm preparation methods
Addition of substances in sperm preparation
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3. Insemination:
1. Number of inseminations
2. Time of insemination
preferably between D13 &16.
3. Number of motile sperms inseminated of more
than 5 million
Couples with <5 million motile spermatozoa inseminated should be referred directly for IVF
CPR/cycle: 5%.
Others have reported that satisfactory CPR is achieved if the motile sperms inseminated is 1 million.
ABOUBAKR ELNASHAR
Cost Effectiveness
initially treatment with IUI
more cost-effective than IVF in most cases of
Unexplained
moderate male subfertility.
(Carceau et al 2002; Ombelet et al 2005)
ABOUBAKR ELNASHAR
CONCLUSION
• IUI
– least expensive
– least invasive
– least stressful
– least hazardous.
• IUI alone
– useful in couples with severe sexual dysfunction
– cervical factor infertility as long as at least one fallopian tube
is patent.
ABOUBAKR ELNASHAR
• ovulation predictor kit to schedule the optimum time
for the procedure.
• For patients with mild male factor, early stage
endometriosis, or unexplained infertility:
superovulation with IUI rather than natural cycle IUI (Grade 2B).
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
4.My clinic: Elthwara St. Mansura
ABOUBAKR ELNASHAR
IUI/COH
simple treatment
good LBR, especially in
younger patients and/or
those with previous parity.
More than 90% of total live births with IUI/COH is
achieved during the first two cycles.
probabilities of success can be used to individualise
treatment decisions and that there is merit in
continuing to offer IUI before resorting to IVF for
certain patients.(Geisler et al, 2017)
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ICSI is more cost effective than IUI when the mean total motile sperm count is <10 million
(Van Voorhis et al,2001)
Male infertility total number of motile spermatozoa (TMSC) < 20 ×106/ejaculated
(Hajder et al, 2016)
ABOUBAKR ELNASHAR
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