Ovarian Stimulation in IUI- Overview
Dr. Jyoti BhaskarMD MRCOG
Director
Lifecare IVF
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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. Recruiting multiple follicles
2. Control timing of ovulation
3. Prevention of premature LH surge
4. To time the insemination
5. Increase the pregnancy rate
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Optimum Ovarian Stimulationfor 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 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)CLOMIPHENE CITRATE ( SERM)
HYPOTHALAMUS ER HYPOTHALAMUS ER
BindsBinds
GnRHGnRH
Pituitary Pituitary
FSHFSH
OVARY OVARY
FolliculogenesisFolliculogenesis
Blocks ERBlocks ER
CervixCervix
EndometriumEndometrium
VaginaVagina
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DOSAGE
• Single dose -- together
• Monitor Cycle with USG
• If ovulation confirmed – maintain same dose
• Max to 150 mg
Starting Dose 100mg day 2 onwards for 5 daysStarting Dose 100mg day 2 onwards for 5 days
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CC FAILURE ( 40%)No Pregnancy 2 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
CC FAILURE ( 40%)No Pregnancy 2 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
2 CYCLES OF CC WITH IUI2 CYCLES OF CC WITH IUI
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CC RESISTANCE (20%)
2 CYCLES OF CC
NO OVULATION
CC RESISTANCE (20%)
2 CYCLES OF CC
NO OVULATION
CC + GONADOTROPHINS
CC + GONADOTROPHINS
GONADOTROPHINSGONADOTROPHINS
COST , PT’S CHOICE
COUNSELLING
COST , PT’S CHOICE
COUNSELLING
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Antioestrogenic Effect
• Thin Endometrium
• Poor cervical Mucus
Start early in cycle – Day 2 or Day 1Add oestradiol valearate from day 8/9
Use all gonadotrophin cycle
Start early in cycle – Day 2 or Day 1Add oestradiol valearate from day 8/9
Use all gonadotrophin cycle
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Gonadotrophins - Indications
CC Resistance
CC Failure
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• HMG• Highly purified Urinary HMG/FSH • Recombinant. FSH
Choice of Gonadotrophins
Day 2 LH/FSHDay 2 LH/FSH
FSHFSH
LH
PCOS
LH
PCOS
FSH
WHO group1
FSH
WHO group1
HMGHMG
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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
MonitoringExperience
Strict protocols
MonitoringExperience
Strict protocols
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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
Protocols
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101112131415
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DAYS OF CYCLE
TVS – ET AND AFC
CC100 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 -VE
Inj HCG 5000 U i/m
Timed Intercourse
8pm stat
IUI
36 hrs later at 8am at Lifecare24hrs later at 8am
Sexual relation at same night and for 2 days
Luteal support – ETV ES/ Susten vaginally at night
Serum Progesterone 7 days after IUI/Ovulation
CC ONLY PROTOCOL -- +/- IUI
B LONG F ONCE DAILY ALL THROUGH OUT THE CYCLE
UPT 18 days after IUI/Ovulation
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Unripe follicle
Ripening follicle
Ovulation Corpus luteum
Regression of Corpus luteum
Clomiphene 100 mg day2
for 5 days
Gonadotrophin stimulation
HCG Leading follicle > 18mm
Oocyte mature
38 hrs
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Days 7 14 21 28
hCG
150 IU 112.5 IU 75 IU hCG
Foll. 10 mm
75-150 U daily
6 12
hCG
Foll. 16mm
Gonadotrophin Regimens
37.5 IU 75 IU 112.5 IU 150 IU
Chronic Low dose Step up regimen
Step down
Conventional Regime
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Gonadotrophins with Antagonists
• Lubek Protocol
• French Protocol
15-20% cycles with Gonadotrophins have premature LH surge
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 IUILow 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.
23The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJThe Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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GnRH-agonists There seems to be no role in IUI programsIncrease costs Increase multiples without increasing the probability of conception
Urinary gonadotrophins versus Recombinant productsThere is no significant difference
GnRH-antagonistsWhether or not are going to play a role in mild ovarian hyperstimulation/IUI programs needs to be determined in future trials.
LetrozoleThere 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 BJThe 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
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