Ovarian Stimulation in IUIOverview
Dr. Jyoti Bhaskar
MD MRCOG
Director
Lifecare IVF
Rationale for COH in IUI
• Increasing the number of eggs available for
fertilisation
• Overcoming subtle defects in ovulatory
function and luteal phase.
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Aim of COH
1.
2.
3.
4.
5.
Recruiting multiple follicles
Control timing of ovulation
Prevention of premature LH surge
To time the insemination
Increase the pregnancy rate
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Optimum Ovarian Stimulation
for IUI

2 – 3 follicles with Ø 18 – 19 mm.

Endometrium  9 mm thick & trilaminar.

IUI between Cycle D13 and D16, 36-40 hrs.
from HCG inj.
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Classification
WHO
• I - Hypothalamic pituitary failure
(Hypogonadotrophic hypogonadism)
Kallman’s, Sheehan’s, anorexia
• II - Hypothalamic pituitary dysfunction
(PCOS)
• III – Ovulatory Failure – Hypergonadotrophic
hypogonadism, Turner’s, autoimmune,
mumps, RT, CT
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Drugs for Ovarian Stimulation
• Clomiphene Citrate,
• Gonadotrophins:
• HMG
• highly purified ur FSH
• Rec. FSH
• GnRH antagonist
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CLOMIPHENE CITRATE
• Most widely
• Simple to use,
 Minimal side effects,
 Cost effective
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CLOMIPHENE CITRATE ( SERM)
Binds
HYPOTHALAMUS ER
GnRH
Blocks ER
Pituitary
FSH
Cervix
Vagina
OVARY
Folliculogenesis
Endometrium
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DOSAGE
Starting Dose 100mg day 2 onwards for 5 days
• Single dose -- together
• Monitor Cycle with USG
• If ovulation confirmed – maintain same
dose
• Max to 150 mg
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CC FAILURE ( 40%)
No Pregnancy
2 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
2 CYCLES OF CC WITH IUI
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CC RESISTANCE (20%)
2 CYCLES OF CC
NO OVULATION
COST , PT’S CHOICE
COUNSELLING
CC +
GONADOTROPHINS
GONADOTROPHINS
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Antioestrogenic Effect
• Thin Endometrium
• Poor cervical Mucus
Start early in cycle – Day 2 or Day 1
Add oestradiol valearate from day 8/9
Use all gonadotrophin cycle
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Gonadotrophins - Indications
CC Resistance
CC Failure
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Choice of Gonadotrophins
• HMG
• Highly purified Urinary HMG/FSH
• Recombinant. FSH
Day 2 LH/FSH
FSH
LH
FSH
PCOS
WHO group1
HMG
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DOSE
•
•
•
•
•
BMI
Ovarian reserve
Age
Cause of Infertility
Dose needed in previous cycle
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Complications
 Multifetal pregnancy
• OHSS - Life threatening
Monitoring
Experience
Strict protocols
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Protocols
1. CC only with TI or IUI
2. CC ± FSH or ± HMG with IUI
3. Gonadotrophin only
n Conventional regime
n Gn. Low dose step-up protocol
n Gn. step-down protocol
4. Gonadotrophin with GnRH antag
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DAYS OF CYCLE
2
3
4
5
6
7
8
9
10
11
12
13
14
15
CC ONLY PROTOCOL -- +/- IUI
B LONG F ONCE DAILY ALL
THROUGH OUT THE CYCLE
TVS – ET AND AFC
CC
100 MG
DAILY
Day 2-6
TVS – FOLLICLE SIZE, ET
IF ET< 5MM OV 2MG BD DAILY
TVS – FOLLICLE , ET , CERVICAL MUCUS
STUDY, POST COITAL TEST
FOLLICLE >20MM -- LH SURGE
+ VE
stat
-VE
Inj HCG 5000 U i/m
8pm
Timed Intercourse
24hrs later at 8am
36 hrs later at 8am at Lifecare
IUI
Sexual relation at same night and for 2 days
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Luteal support – ETV ES/ Susten vaginally at night
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Serum Progesterone 7 days after IUI/Ovulation UPT 18 days after IUI/Ovulation
Unripe
follicle
Ripening
follicle
Ovulation
Corpus
luteum
Regression of
Corpus luteum
Oocyte mature
38 hrs
Clomiphene
100 mg day2
for 5 days
Gonadotrophin
stimulation
HCG Leading follicle > 18mm
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Gonadotrophin Regimens
Chronic Low dose Step up regimen
Days
7
14
hCG
150 IU
112.5 IU
75 IU
37.5 IU
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Step down
112.5 IU
150 IU
75 IU
hCG
Foll.  10 mm
Conventional Regime
75-150 U daily
6
hCG
12
Foll.  16mm
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Gonadotrophins with
Antagonists
• Lubek Protocol
• French Protocol
15-20% cycles with Gonadotrophins
have premature LH surge
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Advantages of Antagonist
Protocol
• Helps avoid IUI at weekends
• Compared to agonist – simple and
inexpensive
• Lower rates of OHSS
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Anti-oestrogens
Cost effective but less effective when compared to gonadotrophins.
Do not prevent multiple pregnancies
Have anti-oestrogenic effect on the endometrium
Gonadotrophins
Most effective drugs for IUI
Low dose protocols (50 to 75 IU per day) are advised
Pregnancy rates do not seem to differ significantly from pregnancy
rates with high dose regimens (> 75 IU per day) whereas the
changes to encounter negative effects from ovarian stimulation,
such as the risk of multiples and the risk of OHSS might be
higher with high dose protocols.
The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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GnRH-agonists
There seems to be no role in IUI programs
Increase costs
Increase multiples without increasing the probability of conception
Urinary gonadotrophins versus Recombinant products
There is no significant difference
GnRH-antagonists
Whether or not are going to play a role in mild ovarian
hyperstimulation/IUI programs needs to be determined in future trials.
Letrozole
There is no convincing evidence that Letrozole is superior to clomiphene
citrate and therefore the cost should be taken into account when using
anti-oestrogens.
The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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Ovarian stimulation protocols
(anti-oestrogens, gonadotrophins with and without GnRH
agonists/antagonists)
for intrauterine insemination (IUI) in women with subfertility
(Review)
The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
Gonadotrophins
might be the most effective drugs with IUI
Low dose protocols are advised
No studies using CC + gonadotrophins
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• There is evidence that IUI with OH increases the live
birth rate compared to IUI alone.
• The likelihood of pregnancy was also increased for
treatment with IUI compared to TI both in stimulated
cycles.
• There is insufficient data on multiple pregnancies and
other adverse events for treatment with OH.
• Therefore, couples should be fully informed about
the risks of IUI and OH as well as alternative
treatment options.
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Conclusion
• Choice depends on doctors expertise
and patients condition, choice
• Gonadotrophin only protocol offers
the best success rate
TIME TO MOVE ON TO TOTAL GONADOTROPHIN CYCLE
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Ovarian Stimulation protocol
• Simple
• Cost Effective
• Minimal side effects
• Best success rates
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Thank you
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