This slide deck is prepared keeping in view the need of understanding the procedure of IUI (Intrauterine Insemination). Being a professional working in the field of infertility management, it was very difficult for me to find such material on IUI in which all the relevant information is gathered on one yet to the point and concise platform. So I developed this presentation to help you guys. My role was to gather the relevant data in one simple yet elaborate presentation. Nothing in this presentation is personally written by me, so I have mentioned the references very clearly. I hope the readers will find it very useful. Intrauterine insemination (IUI) is a procedure that involves placing sperm inside a woman’s uterus to facilitate fertilization. This fertility treatment does not involve the manipulation of a woman’s eggs, and therefore is not considered an assisted reproductive technology (ART) procedure.

1. Physician’s Training Module
Dr. Sarwat Jabeen
MBBS, MBA Health Management & Pharmaceutical Marketing
Product Manager – Fertility

2. Intrauterine insemination (IUI) is a form of treatment where
sperm are inserted into the uterine cavity around the time of
ovulation.
IUI can be carried out in a natural cycle, without the use of
drugs, or the 5 ovaries may be stimulated with oral antiestrogens or gonadotrophins.
1. NICE Guidelines - 2012

3. The procedure allows one to bypass the cervix to deposit sperm
closer to tubal ostium, thereby facilitating a larger number of motile
sperms to reach the fertilization site in the ampulla of fallopian
tube.
In addition, the sperm separation procedure would remove WBC,
dead and moribund sperms generating free oxygen radicals which
reduce the functional capacity of intact sperms.
Components in the media also induce gentle capacitation of sperm
which is necessary to make them functionally ready for fertilization.
Controlled ovarian stimulation is often used in conjunction with IUI
treatment which also enhances the chance of pregnancy by
inducing multiple ovulation.

4. Where drugs are used to stimulate a cycle, in the case of oral antiestrogens a woman will take a course of tablets for 5 days.
With gonadotrophins (E.g. rFSH-Puregon) the woman usually
receives a course of daily fertility injections for 7 to 10 days.
However, the exact duration of stimulation will depend on which
day of the cycle it is started.
In both circumstances the treatment should be monitored by
ultrasound scan to assess the ovarian response.
1. NICE Guidelines - 2012

5. When one to three follicles are seen to have developed to a
suitable size, usually with one dominate follicle, then an injection of
hCG is given which triggers ovulation.
Insemination of prepared sperm will be undertaken 24 to 36 hours
later. However, in order to reduce the risk of multiple pregnancies if
more than three follicles have developed or two or more mature
follicles are seen then insemination may not be undertaken.
1. NICE Guidelines - 2012

7. Unexplained infertility
Mild endometriosis
Mild male factor infertility
Disability (physical or psychological) preventing vaginal sexual
intercourse
Conditions that require specific consideration in relation to
methods of conception (such as after sperm washing in a couple
where the male is HIV positive)
Fertility preservation
As part of donor insemination
IUI in stimulated cycles may be considered while waiting for IVF, or
when in women with patent tubes IVF is not affordable.
1. NICE Guidelines – 2012. 2. Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. IUI – The ESHRE Capri Workshop Group

8. IUI is contraindicated in women with:
Cervical atresia
Cervicitis
Endometritis
Bilateral tubal obstruction
In most cases of amenorrhea or severe oligospermia
1. Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. IUI – The ESHRE Capri Workshop Group

9. Female age <40 years
Minimum of 1.5 years of infertility
Patent
fallopian
tubes
confirmed
by
laparoscopy
hysterosalpingogram
Presumptive proof of ovulatory cycle
Ultrasound evidence of mature follicles & ovulation
Luteal phase progesterone (P) cutoff >35 nmol/L
/
Male partner:
Two semen analysis revealing at least 10 million recovered motile
sperm / whole sample

10. Patient with any of the following diagnosis could be
considered for IUI treatment:
Unexplained infertility
Male factor
Immunological factors
Cervical factors

11. Proper indication
Satisfactory semen analysis
Patent, healthy fallopian tubes
Need to increase FSH threshold in early follicular phase with either
oral ovulation inducing agent and / or injections of exogenous
gonadotropin preparations (E.g. Puregon)
Identify or preempt the spontaneous LH surge

12. Detailed clinical history of both partners
Counseling for IUI procedure
Detail explanation of the technique, risk, complications and expected
outcome.
Examination of the Female Patient
Physical examination and local
Transvaginal Sonography
Day-21 serum progesterone
Tubal assessment by laparoscopy / hysterosalpingogram
If the patient has got irregular menstruation – baseline hormones
should be done

14. Poor results have been described when IUI was performed in natural cycles for
unexplained and cervical factor.
The rationale behind the use of ovarian hyperstimulation in artificial
insemination is the increase of the number of oocytes available for fertilization
and to correct subtle unpredictable ovulatory dysfunction.
Drugs for OI in IUI:
Oral
Anti-estrogens (Clomiphene Citrate – Ovafin®) 50 – 100 mg for five days
Aromatase Inhibitors (Letrozole) 2.5 – 7.5 mg for five days
Injectables
hMG 75 – 150 mg / day from day 3 – 7 of cycle
FSH – uFSH or rFSH (E.g. Puregon®) 75 – 150 mg / day from day 3 – 7 of cycle
hCG (E.g. Pregnyl®) 5000 – 10,000 IU for follicle puncture and to time
insemination
1. Human Reproduction 2008. Intrauterine insemination (IUI) as a first-line treatment in developing countries and methodological aspects that might influence IUI success. 2. Ovarian
stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility (Review). Copyright © 2011
The Cochrane Collaboration.

15. The drugs for OI in IUI – A Comparison:
Intra-uterine insemination combined with OH has been proven effective for
couples with unexplained and mild male factor subfertility.
Compared with IVF, IUI with OH is less invasive and more cost-effective .
Antiestrogens Vs. Gonadotropins
In the 2007 Cochrane review of seven trials, the results demonstrated that in an IUI
program, ovarian stimulation with gonadotrophins increases pregnancy rates per
couple significantly, compared to anti-oestrogens, without effecting adverse
outcomes.
Antiestrogens Vs. Aromatase Inhibitors
In the 2007 Cochrane review of five studies, None of the trials solely or in
combination provided convincing evidence of a significant difference.
1. Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility (Review).
Copyright © 2011 The Cochrane Collaboration.

16. WHO Reference Values
Reference Limit
Semen volume (ml)
1.5
Sperm concentration (106/ml)
15
Total sperm number (106/ejaculate)
39
Progressive motility (PR, %)
32
Total motility (PR +NP, %)
40
Vitality (live sperms, %)
= / > 58
Sperm morphology (NF, %)
=/>4
pH*
= / > 7.2
Leucocyte* (106/ml)
<1
MAR/Immunobead test* (%)
<50
1. WHO 2010 laboratory manual for the Examination and processing of human semen

17. Screening for anti-sperm antibodies should not be offered because there is
no evidence of effective treatment to improve fertility.
If the result of the first semen analysis is abnormal, a repeat confirmatory
test should be offered.
Repeat confirmatory tests should ideally be undertaken 3 months after the
initial analysis to allow time for the cycle of spermatozoa formation to be
completed. However, if a gross spermatozoa deficiency (azoospermia or
severe oligozoospermia) has been detected the repeat test should be
undertaken as soon as possible.
Concerning the insemination sample, the recommended lower limit ranges
from 3 million motile sperm to 5 million to 10 million
The routine use of post-coital testing of cervical mucus in the investigation
of fertility problems is not recommended because it has no predictive value
on pregnancy rate.
NICE Guidelines 2013

18. The semen is a mixture of motile and dead spermatozoa with cells, cellular
debris and sometimes micro-organisms present.
Prior to IUI, it is necessary to remove seminal plasma to avoid
prostaglandin-induced uterine contractions.
Insemination with unprocessed semen is also associated with pelvic
infection.
A variety of methods have been developed to separate the motile sperms
from the ejaculate. The most common methods are washing and
centrifugation which has been shown to cause some damage to the sperm.
Simple sperm wash
Swim up
Gradient
All preparations should done in a laminar flow for sterility.
The clean sperm suspension is used for IUI, IVF and ICSI and certain special
sperm tests.
1. Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. IUI – The ESHRE Capri Workshop Group. 2. WHO 2010 laboratory manual for the Examination and processing of human semen

19. Simple Sperm Wash
This method is used if the semen sample is very poor. It mainly removes
seminal plasma from the sperms.
One volume of semen is placed in a 15 ml test tube and diluted with 2
volume of culture medium. The tube is gently inverted twice to mix the
components.
The tube is then centrifuged at 250-300g for 5-7 min.
The supernatant is removed and the pellet is re-suspended in 2 ml of
culture medium.
The centrifugation is repeated at 250-300g for 5-7 min and the supernatant
removed. About 0.4 ml of media is added to the final sperm pellet for resuspension.
The sample is suited for intra-cervical insemination
WHO 2010 laboratory manual for the Examination and processing of human semen

20. Swim Up Method
This technique relies on the ability of the sperms to swim. This method is
suitable for semen with high to moderate motility.
Semen is diluted with 1:2 ratio of culture medium and centrifuged at 250300g for 5-7 min.
The supernatant is removed leaving the pellet.
Pipette 0.8-1 ml of media into a new test tube. Carefully layer the semen
pellet beneath the media.
Stand at 37o for 45-60 min. Placement of tube at 45oangle creates a larger
surface area for sperms to swim-up.
Carefully take up the top 0.5-0.6 ml without disturbing the lower layer and
transfer into a new test tube.
To concentrate the sperms, pooled several tubes and centrifuged at 250300g for 5-7 min. The supernatant is removed and the resultant pellet resuspended in 0.4 ml of media.
WHO 2010 laboratory manual for the Examination and processing of human semen

21. Gradient Systems
Gradient systems use solutions with a higher density than semen to
separate the debris, cells, micro-organisms and non-motile sperms from the
motile ones.
Commercially available dense solutions used are colloidal silica (Percoll,
Puresperm), poly-sucrose (Ficoll, Ixaprep) and other dense solutions
(Optiprep, Nycodenz).
Centrifugal force is applied to enable the motile sperms to swim from a less
dense seminal fluid into a denser solution.
Cellular debris and non-motile microorganisms will be trapped at the
interphase between the two solutions
Select more normal sperms than swim up method.
Recovery may be poor in viscous semen and severe teratozoospermia (small
heads but good swimmers)
WHO 2010 laboratory manual for the Examination and processing of human semen

22. Quality of the Specimen
• There is no consensus on a lower limit of semen quality at which one would
advocate ICSI rather than IUI.
• It has been reported that pregnancy rates are lower if the semen sample
contains ,10 million sperm in total.
• Concerning the insemination sample, the recommended lower limit ranges
from 3 million motile sperm to 5 million to 10 million.
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

23. • The sperm suspension can be deposited in the cervix, the uterus, the
peritoneum or the Fallopian tube.
• IUI is by far the most common method.
• It is performed by introducing a 0.2–0.5 ml sperm suspension into the
uterus with a small catheter, usually without imaging guidance.
• With Fallopian tube sperm perfusion (FSP), the inseminate is 4 ml, so that
with this large volume of fluid the inseminate may fill not only the uterine
cavity and Fallopian tubes, but also some of the volume may even end up
inside the peritoneal cavity.
• For frozen semen, IUI is better than intracervical insemination (ICI): the
likelihood of live birth after six insemination cycles is 2-fold higher (OR:
1.98; 95% CI: 1.02–3.86) (Besselink et al., 2008).
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

24. • In two trials among patients with unexplained infertility, results with FSP
were better than with IUI (Kahn et al., 1993; Cantineau et al., 2003).
• For other indications, there is not sufficient data to suggest that FSP is any
better than IUI.
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

25. • Insemination can be done at various time points around ovulation and can
be done once or several times.
• In the majority of the published studies, the insemination is done 32–36 h
following hCG administration.
• It is assumed that the timing of insemination relative to ovulation is critical
for an optimal success rate.
• A systematic review found no difference in the pregnancy rate per couple
with two inseminations compared with one (Cantineau et al., 2003).
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

27. IUI in an Office Setting
IUI is done as an office procedure by gynecologists in private practice.
They use the services of the nearby ultrasound centers for follicular tracking
and of specialized IUI laboratory for sperm preparation.
In case of any complication, patients are transferred to a specialized
hospital.
Good coordination between gynecologist, sonology lab and IUI lab is
required to make this setup successful.
IUI within a General Hospital
IUI is done by gynecological consultants.
Laboratory and ultrasound services are available in respective departments
for follicular tracking and semen preparation.
Disadvantage is sonologist may not have adequate training in follicular
tracking and semen preparation in a general laboratory may result in
suboptimal results.

28. IUI within an IUI Clinic
All IUI services re provided under one roof.
Initially the unit may start only as IUI clinic but may later commence other
treatments of ART.
This should be kept in mind when planning IUI clinic so that space for
expansion to create a future ART center in same premises is available.
IUI within ART Center
This IUI setup is in a specialized ART laboratory.
The appropriate equipments, media, drugs and staff are already in place
and no separate requirements need to be filled.

29. Room for IUI Laboratory
The room should be as close as possible to procedure room.
The room must have its own air conditioning.
There must not be any free access to any toxic fumes.
Sufficient space to accommodate necessary equipments.
During insemination it is vital that clinician is able to communicate
with lab personnel.
There must be suitable facilities for sperm preparation.

30. 1. Semen Assessment & Sperm
Preparation
Meckler counting chambers
Microscope
phase
contrast
microscope with resolving power
4,10,40,100 with eye piece 10x.
Centrifuge machine with swing-out
rotor, timer and RPM meter
5% CO2 incubator with 37C with
gas cylinder
Laminar flow hood (horizontal /
vertical)
Wide mouth sterile semen
collecting jar
Integrated Laminar Flow
IUI Workstation

31. 2. Semen Assessment & Sperm Preparation
Sterile test tubes
Sterile conical / round bottom tubes
Pipette
Pipette pump
Test tube rack
Media
Good light source
CASA system
CASA System

32. 3. Gynecological Equipment
Cusco’s speculum
IUI catheter
1 ml syringe
Uterine sound
Cervical dilator 5/6 mm
Tenaculum single toothed
OT light
Ultrasound machine with transvaginal probe

33. 4. Media
Flushing media
Culture media
Sperm preparation media
Cryopreservation media
5. Record Keeping and Documentation
6. Maintenance of Equipment
Incubator should be checked daily in the morning for temperature
Internal water reservoir of the incubator should be cleaned regularly
Laminar flow should be cleaned periodically with 70% isopropyl
alcohol
Gas cylinder should be checked regularly to check for any leakage
7. Quality Control Methods & Laboratory Asepsis should be in place

34. Physical Structure & Floor Plan

35. 1. Reception Enlistment Area
2. Waiting Area
3. Subfertility Clinic Area
4. Male clinic Area
5. Sperm Collection Room
6. Andrology Laboratory
7. Receiving area
8. Main laboratory

36. 9. IUI Procedure Room
Patient bed
Cusco’s speculum
Disposable rubber sheet
Disposable per vaginal gloves
Swab holding forceps
Volsellum
10. Doctor’s Office
11. Transvaginal Ultrasonography Room

38. Diagram showing the
many different variables
influencing success rates
in IUI programs (AIH,
artificial insemination with
homologous semen).
1. Human Reproduction 2008. Intrauterine insemination (IUI) as a first-line treatment in developing countries and methodological aspects that might influence IUI success.

39. Age of the female
Indication for IUI
Use of controlled ovarian stimulation
The processed total motile sperm count in the inseminate
Practical Issues Involved in Enhancing Pregnancy Outcome in
IUI
Duration of subfertility
Parity
Pre-IUI semen report
Number of IUI cycles attempted

40. Practical Issues Involved in Enhancing Pregnancy Outcome in
IUI (contd.)
Number and size of dominant follicle
Blood estradiol concentration on hCG day
Endometrial thickness at scan on hCG day
Doppler blood flow studies of follicles / endometrium
Practical issues at IUI:
Type of IUI catheter
Fresh or frozen-thawed sperm
Post-processing sperm morphology / motility grade
Timing of IUI in relation to hCG administration

41. Practical Issues Involved in Enhancing Pregnancy Outcome in
IUI (contd.)
Practical issues at IUI (contd.):
Number of IUIs
Volume of inseminate used
Time to rest following IUI procedure

42. 1. For people with unexplained infertility, mild endometriosis or mild
male factor infertility, who are having regular unprotected sexual
intercourse:
– do not routinely offer intrauterine insemination, either with or
without ovarian stimulation
– advise them to try to conceive for a total of 2 years (including up to 1
year before investigation) before IVF will be considered.
1. NICE Guidelines - 2012

43. 2. Consider unstimulated intrauterine insemination as a
treatment option in the following groups as an alternative to
vaginal sexual intercourse:
– people who are unable to, or would find it very difficult to have vaginal
intercourse because of a clinically diagnosed physical disability or
psychosexual problem who are using partner or donor sperm;
– people with conditions that require specific consideration in relation
to methods of conception (for example, after sperm washing where
the man is HIV positive)
– people in same-sex relationships.
1. NICE Guidelines - 2012

44. 3. For people in recommendation 2 who have not conceived
after six cycles of donor or partner insemination, despite
evidence of normal ovulation, tubal patency and semen
analysis, offer a further six cycles of unstimulated intrauterine
insemination before IVF is considered.
1. NICE Guidelines - 2012

45. • In good prognosis couples, the live birth rate is better without
treatment.
• IUI is widely used with infertility diagnoses other than
bilateral tubal obstruction, severe male infertility and severe
ovulation defects.
• Differences in sperm preparation and IUI methodology do not
have profound effects on the success rate.
• Prior to using IVF, IUI with clomiphene ovarian stimulation is
relatively cheap and many couples will conceive and not
require IVF.
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

46. • IUI in stimulated cycles was effective only in patients with
more than 3 years duration of infertility but is associated with
a significant rate of higher-order multiple births.
• Prevention of premature LH surges and luteal phase support
do not appear major requirements in IUI cycles.
• Although IUI treatment is cheaper and less demanding on the
patient, IVF is the most effective treatment for infertility.
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009. Intrauterine insemination. The ESHRE Capri Workshop Group.

47. NICE Guidelines 2012, 2013
Intrauterine insemination. The ESHRE Capri Workshop Group.
Human Reproduction Update, Vol.15, No.3 pp. 265–277, 2009.
WHO 2010 laboratory manual for the Examination and processing of
human semen
IUI Intrauterine Insemination
By Chakravarty Mukherjee
Manual on IUI: What, When and Why
By Nusrat Mahmud, Narendra Malhotra, MalhotraJaideep