INTRAUTERINE INSEMINATION
Dr Jyoti Gupta
Amrit IVF Center
Hospital Amritdhara
Karnal
WHAT IS IUI
●IUI is deliberate introduction of sperms in the female uterus
in order to achieve pregnancy
●One of the simplest techniques of ARTs
●Minimally invasive and uncomplicated procedure
●First therapeutic step in treatment of infertility
●Cost-effective, simple, can be learned easily
●Husband or Donor sperm (frozen and quarantined) can be
used.
RATIONALE OF IUI
3 Components which help in improving the result
1. SEMEN PREPARATION
●Selects the most active sperm fraction, removing the debris,
prostaglandins, leucocytes & antigenic proteins
●The media provides nutrition & improves motility
●Helps in capacitation
2. COH
●More oocytes available
●Subtle endo disorders corrected
●Accurate timing of ovulation
3. INTRAUTERINE INSEMINATION
●Bypasses cx barrier, anatomical defects, inc density of sperms in
uterus
FRESH/FROZEN?
●Results better with fresh
washed sperm
●Frozen quarantined
recommended by ART law
(to eliminate the risk HIV,
HbsAg etc.)
●Donor anonymous.
STEPS OF IUI
●Pretreatment workup
●Counselling for IUI
●Ovarian Stimulation
●Monitoring of response
●Ovulation trigger & Timing of IUI
●Semen collection
●Sperm preparation
●Insemination
●Post insemination follow up
PRE-TREATMENT WORK UP
PRETREATMENT WORK UP
●Assess ovulation status- Follicular study
●Tubal status- HSG
●Hormonal Status- PRL & TSH are done routinely. Others are FSH,
LH, E2, Testosterone, DHEAS, D21 Serum Progesterone
●Semen report (>10M/ml)
●Exclude Fibroids, Polyps,
● Tuberculosis, Hydrosalpinx, Endometriosis etc.
●Screen for VDRL, HIV, HbsAg, HCV
●Bl Sugar, Serum Insulin (Severe PCO), Bl Group
●Both partners must be screened
●Rubella IgG
COUNSELLING OF CASES
COUNSELLING OF CASES
●Indication of IUI
●Timing & No of visits reqd
●Cost involved
●Chances of success
●What is sperm preparation
●Technique of insemination
●Any pain
●Role of rest
●Assurance on mix-up & confidentiality
CONTROLLED OVARIAN
HYPERSTIMULATION
4 categories of patients
1. Normally ovulating subjects-- Indication is male factor
2. Normally ovulating (Unexplained Infertility)
3. Anovulatory subjects eg
- PCO-
- Other Endocrinological disturbances
4. Hypo Hypo
Aim is to have 2-3 DF maesuring >18mm at the time of trigger.
OVARIAN STIMULATION
Will depend upon her indication, ovulatory status and pt's
affordability.
The response to previous cycle also helps us decide the regime
●Natural cycle
●CC/Letrozole stimulated cycle
●Gonadotrophin stimulated cycle
●CC + GTN
●Down regulated cycle
NATURAL CYCLE
If the pt has normal ovulatory cycles
Fault lies mainly with male partner
●BBT
●LH Surge from D9, when positive, do IUI after 24 hrs
●TVS from D9- When DF 20mm, can give HCG to trigger
ovulation----- IUI after 36 hrs
ORAL OVULOGENS (CC/LET)
●In PCOs, Unexplained Infertility,
●CC 50-100mg from D2/3 x 5d
●Letrozole 2.5-5mg from D2/3x 5d, 2.5 from D2 x 10d, or daily
increasing dose
●Starting later than D3 is bad for Endometrium & gives lesser no.
of follicles
●Monitor the progress on TVS----When DF is 20mm, give HCG
trigger.
GONADOTROPHINS
In PCOs, Unexplained Infertility, Mild subtle Endocrinological
defects, Hypo Hypo.
Various preparations available depending upon their content, purity,
efficacy & cost. Various generations of GTN are:
1. HMG (FSH+LH)
2. Purified FSH
3. Ultra-purified FSH
3. Re-FSH (Cultured in Hamster Ovarian cells)
Adv of purified/recombinant: No urinary impurities, Batch to batch
consitency, s/c use, self administration, less dose, more oocytes,
higher preg rate.
PROTOCOLS of GTN
STEP UP- Start with 75IU/d x 5d
Increase to 150IU/d if no response till DF >18mm
Give HCG 5-10,000IU
IUI after 36hrs
STEP DOWN-
Start with 150-225IU/d
reduce the dose to 75IU/d when DF >12mm
HCG when DF>18mm
CC+ GTN
●CC 50-100mg D2-D6
●HMG/FSH/Re-FSH 75-150IU from D6,7,8
●Proceed acc to response on U/S from D9
●HCG when DF>18mm
DOWN REGULATION CYCLES
●Agonist DR
●Antagonist DR
●Ovulation time becomes very predictable and can time the
Insemination correctly
●Very expensive
●Pregnancy rates better, though not very encouraging, so not cost
effective
MONITORING OF AN IUI CYCLE
MONITORING OF IUI CYCLE
●D2- TVS to look for a CYST, ET, AFC
●Hormone tests- FSH, LH, E2
●From D9, repeat TVS to see the no. of follicles, size, ET. E2
levels if felt necessary
● When DF >17, repeat E2 (250pg/DF) on day of trigger
●BBT
●LH Kits
●LH level for premature LH surge
OVULATION TRIGGER & TIMING
OVULATION TRIGGER & TIMING OF IUI
HCG 5000 or 10,000 units or GnRHa .5 s/c or Re-LH 250 units
When DF is
●Natural cycle- 22mm
●CC- 20mm
● CC+GTN- 18mm
●Re-FSH- 16mm
& ET >8mm
IUI done after 36 hrs. (once)
Or, twice after 18-24hrs and 36-48 hrs.
WITHHOLD TRIGGER
●HCG- if 4 follicles >16mm
●GnRHa- if 8 follicles >12mm
●Re-LH 250IU is preferred when OHSS is suspected.
SEMEN COLLECTION
SAMPLE CONSENT FORMS E&F
●FORM – F
●Consent for Artificial Insemination or Intrauterine Insemination with
●Donor Semen (See Rule 15.1)
●We,__________ and _________, being husband and wife and both of
legal age, authorize Dr.____________to inseminate the wife
artificially or intrauterine with semen / sperm of a donor (ART bank’s
●no._______; obtained from ________ART bank with valid
registration no……………….) for achieving conception.
●We understand that even though the insemination may be repeated as
often as recommended by the doctor, there is no guarantee or
assurance that pregnancy or a
●live birth will result.
●
●We have also been told that the outcome of pregnancy may not be the
same as
●those of the general pregnant population, for example in respect of
abortion, multiple
●pregnancies, anomalies or complications of pregnancy or delivery.
●
●We declare that we shall not attempt to find out the identity of the
donor.
●
●I, the husband, also declare that should my wife bear any child or
children as a
●result of such insemination(s), such child or children shall be as my
own and
●
SEMEN COLLECTION
●Collected in Semen collection
room
●Equipped with Sildenafil
tablets, vibrator, electric
stimulators, erotic magazines
& TV to show erotic movies
etc
DIRECTIONS FOR SEMEN COLLECTION
●Abstain I/C 48 to 72 hours before IUI
●Abstain from alcohol
●Semen sample to be collected at the center
●Sample to be collected in the container provided by ART
laboratory
●Sample should be given by masturbation under strict hygienic
conditions
●Sample should be labeled carefully with patient's name, date and
time of collection
●Avoid exposure to extreme heat and cold
SPERM PREPARATION
IUI LAB
●Clearly defined rooms as prescribed by ART Law
●Semen collection room with attached toilet
●Andrology Lab with a single entry point
●IUI procedure room
●Storage room
●Record room
●Storage of cryocans & Liquid N2 cylinders
●Refrigerator to keep media
●Counseling room, waiting area
AN IDEAL IUI LAB
EQUIPMENT
●Laminar Air flow- Vertical Air flow
●Microscope- x10, x20, x40. With heat stage to maintain temp at
37 degrees.
●Makler Chamber- .01mm deep & sperms are seen in only one
layer
●Centrifuge REMI R8C
●Incubator/Hot Air Oven- To maintain temp, humidity & pH
●Cryocans (Liquid N2 Cylinders)
TYPES OF MEDIA
●Single Layer Density gradient
●Double layer Density
gradient
●Wash media / HAM F10 /
EBSS
●Cryo preservation media
SEMEN ANALYSIS
●Stored at 37 degree in an
Incubator
●Studied after liquefaction
(n 20min)
●Thoroughly mix, no
frothing
●Color
●Odour
●Volume
●Viscocity
●pH (7.2-8)
●Count
●Moltility
RPL
Slow Sluggish
Non-progressive
Immotile
●Morphology
●Other cells – Leukocytes,
Immature germ cells,
epithelial cells, RBCs,
debris
COUNTING IN MAKLER CHAMBER
NORMAL SEMEN VALUES
●According to latest WHO guidelines from 01/10/2011, these are
●Vol >1.5ml
●Total Sperm Count >40m
●Sperm Concentration >20m/ml
●Progressive motility >32%
●Normal Morpholgy >4%
●Live Spermatozoa >58%
●PH >7.2
WHY SPERM PROCESSING?
●To remove the seminal plasma, dead sperms, debris, round cells
●To concentrate the more active sperms
●To improve their motility
●Role of free oxygen radicals ROS
METHODS OF SPERM PREP
●Aim is to separate the spermatozoa from seminal plasma using
minimal mechanical force
●1. Semen wash
●2. Swim up technique
●3. Density gradient method- single layer
- double layer
●Mixing of 2 methods
●Method will be decided by seeing the semen report
SWIM UP TECHNIQUE
DENSITY GRADIENT TECHNIQUE
MIXED TECHNIQUE
SELECTION OF PROCESSING METHOD
●If M S> 50 – 60M ,Sample is not viscous---- Swim up technique can
be used
●In all other cases e.g. Oligozoospermia, Pus Cells, Immature cells,
Round cells---- DENSITY GRADIENT technique is method of
choice
●If motility of sperm is affected by mid piece defect ,derivatives like
pentoxyphylline and caffeine can be added to the medium
INSEMINATION
INSEMINATION
.4 to .6ml of solution containing 5-20m/ml is introduced in the uterus
Foot end of the table is kept raised
Pt discharged after 20 minutes
LIVE IUI PROCEDURE WILL BE SHOWN TO YOU LATER.
POST INSEMINATION FOLLOW UP
POST INSEMINATION FOLLOW UP
1. Luteal support in the form of
Micronized Progesterone (P4) / Duphaston / Inj HCG
2. There is no need for rest, restriction of activity,dietary modifications.
3. I/C is not restricted.
4. UPT is advised 15 days after IUI.
LUTEAL PHASE SUPPORT
Progesterone given in various forms
●Micronized P- Oral / Inj / Vag tablets / Vag Gel
●Oral & Vaginal (100-400mg)OD
●Inj P4 50-100mgIM/OD
●Duphaston 10mg TDS
●Inj HCG 2000-5000IU/3-5D
Natural cycles- not required
CC cycles- Mic P4 100BD
GTN cycle- Mic P4 200BD
Downregulated cycles Mic P 400BD
VARIOUS SITUATION
●1-2 Follicles 400P4
●2-5 Follicles 400P4 + 4mg E2
●>5 Follicles Cancel cycle
●Inj GnRH trigger 400P4 + 6mgE2
●Hypo Hypo 400P4 + 6mgE2 + 2000HCG/5days
To start after how many days?
●GnRH trigger LPS 2 days after trigger
●HCG trigger LPS 5 days after trigger
SIDE EFFECTS OF IUI
●CRAMPING
●INFECTION
●OHSS
●MULTIPLE PREGNANCY
●PSYCOLOGICAL COMPLICATIONS
OVARIAN HYPERSTIMULATION
(OHSS)
●A rare complication of ovarian stimulation for ARTs
●OVARIAN ENLARGEMENT WITH MULTIPLE CYSTS & FLUID
SHIFT INTO E/VASCULAR COMPT.
Grades
1. Abd discomfort & distension
2. Gr 1 + Nausea, Vomiting, Diarrhoea, Ov size 5-12cm
3. Gr 2 + Ascites
4. Gr 3 + Hydrothorax, breathing difficulty
5. Gr 4 + Haemoconc., Coagulation disorders, Renal failure, Shock,
Electrolyte Imbalance.
OHSS
●Etiology: There is increased angiogenesis & Increased permeabilityin
ovaries & surrounding vasculature.
HCG, estrogens, Prolactin, PG etc are implicated for this
As a result, Vasoactive substances like Interleukin, TNF, Endothelin
&VEGF secreted by ovaries.
●Risk Factors- Age 35, Thin, Tall, Low BMI, High E2, multiple
medium size follicles, use of HCG
●Prevention: Low doses of GTN, Close monitoring, Mrtformin, Use of
GnRH instead of HCG, Cabergoline .5mgOD
●Treatment: I/V Fluids, maintain I/V comptt & Electrolyte
balance,Albumin, Hestar, Enoxaperin,Ascitic tap etc.
FACTORS AFFECTING RESULTS
●Age of female partner
●Stimulation protocol used
●Cause of infertility
●Recovery of motile sperm fraction
●Results may vary between 5-30%
Results in various situations
●Natutal cycle + IUI
●CC+IUI
●CC+HMG+IUI
●HMG/FSH+IUI
●DownReg+FSH+IUI
Results- vary between 5%-30% from one end of spectrum to
the other
TROUBLE SHOOTING IN IUI
●How many cycles?
●What to do with thick/viscous semen?
●What to do with poor endometrium?
●How many IUIs per cycle?
SIDE EFFECTS OF IUI
●CRAMPING
●INFECTION
●OHSS
●MULTIPLE PREGNANCY
●PSYCOLOGICAL COMPLICATIONS
CRYO PRESERVATION OF SEMEN
Preserving of semen in live condition at such low temp (-196 C) that the
entire metabolism comes to a standstill.
INDICATION OF CRYO
●Preservation of semen when a person's integrity is threatened
●Before Chemo, radiotherapy, Anabolic Steroids
●Before Vasectomy
●Working husbands away from home
●Neurological diseases
●Stress during the procedure
●Accumulation of semen in oligozoo
● Donor Insemination
DONOR INSEMINATION
●Azoospermia
●Severely subnormal semen parameters
●h/o Hereditary disease in family
●Rhesus Isoimmunization
●IVF/ICSI unaffordable for the pt
●Persistent IVF/ICSI failure
Why Frozen samples only?
●Only Semen Banks to provide the sample
●Selection criteria must be met
●Screened for STDs (VDRL< HbSAg, HIV, HCV)
●One time screen not sufficient to R/O HIV, Hepatitis
●Quarantine for 6 months, retest the donor & release the sample
●Blood Group & Physical Characters can be matched
CONCLUSION
●IUI is an effective, non-invasive, simple & inexpensive method
of treatment
●Careful selection of pts is important
●Young women with patent FT, no ovulation disorders, no
Endometriosis, no severe male factor
●Good counselling is very imp.