1. Ovarian Stimulation in IUI- Overview
Dr. Jyoti Bhaskar
MD MRCOG
Director Lifecare IVF

2. Rationale for COH in IUI
Increasing the number of eggs available for fertilisation
Overcoming subtle defects in ovulatory function and luteal phase.

3. Aim of COH Recruiting multiple follicles Control timing of ovulation
Prevention of premature LH surge
To time the insemination
Increase the pregnancy rate

4. Optimum Ovarian Stimulation
for IUI
2 – 3 follicles with Ø 18 – 20 mm.
Endometrium  8 mm thick & trilaminar.
IUI between Cycle D13 and D16, hrs. from HCG inj.

5. 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

6. Drugs for Ovarian Stimulation
Clomiphene Citrate, Tamoxifen
Gonadotrophins:
HMG
Highly purified urinary FSH
Recombinant. FSH
GnRH Agonist/ Antagonist

7. CLOMIPHENE CITRATE Most widely Simple to use, Minimal side effects,
Cost effective

8. CLOMIPHENE CITRATE ( SERM)
Binds
HYPOTHALAMUS ER
GnRH
Blocks ER
Pituitary
FSH
Cervix
Vagina
OVARY
Endometrium
Folliculogenesis

9. 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 days

10. CC CHECK Evaluation of the patient on Day 2 Previous cycles
TVS – ET , AFC and cysts
Review reports of FSH, LH if available

11. WITH OVULATION AND TIMED INTERCOURSE
CC FAILURE ( 40%)
No Pregnancy
3 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
2 CYCLES OF CC WITH IUI

12. CC RESISTANCE (20%) 3 CYCLES OF CC NO OVULATION
Wt loss, extended CC, adjuvants – metformin, dexamethasone
COST , PT’S CHOICE
COUNSELLING
CC +
GONADOTROPHINS
GONADOTROPHINS

13. 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

14. Gonadotrophins - Indications
CC Resistance
CC Failure
WHO 1

15. Choice of Gonadotrophins
HMG
Highly purified Urinary HMG/FSH
Recombinant. FSH
Day 2 LH/FSH
FSH
WHO group1 LH
PCOS
FSH
HMG

16. DOSE BMI Ovarian reserve Age Cause of Infertility
Dose needed in previous cycle

17. Complications Multifetal pregnancy OHSS - Life threatening Monitoring
Experience
Strict protocols

18. Protocols CC only with TI or IUI CC ± FSH or ± HMG with IUI
Gonadotrophin only
Conventional regime
Gn. Low dose step-up protocol
Gn. step-down protocol
4. Gonadotrophin with GnRH antag

19. IF ET< 5MM OV 2MG BD DAILY3 4 5 6 7 8 9 10 11 12 13 14 15 21
DAYS OF 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 VE
Inj HCG 5000 U i/m
Timed Intercourse
8pm
stat
IUI
36 hrs later at 8am at Lifecare
24hrs 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

20. Regression of Corpus luteum
Unripe follicle
Ripening follicle
Ovulation
Corpus luteum
Regression of Corpus luteum
Oocyte mature
38 hrs
HCG
Clomiphene 100 mg day2 for 5 days
Gonadotrophin stimulation
Leading follicle > 18mm

21. Gonadotrophin Regimens
Chronic Low dose Step up regimen
150 IU
112.5 IU
hCG
37.5 IU
75 IU
Days 7 14 21 28
Step down
150 IU
112.5 IU
75 IU
hCG
Foll.  10 mm
Conventional Regime
U daily
hCG 2 6 12
Foll.  16mm

22. Gonadotrophins with Antagonists
15-20% cycles with Gonadotrophins
have premature LH surge

23. Advantages of Antagonist Protocol
Helps avoid IUI at weekends
Prevents premature surge
Compared to agonist – simple and inexpensive
Lower rates of OHSS

24. The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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 24

25. The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
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

26. might be the most effective drugs with IUI
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 26

27. 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. 27

28. Conclusion Ovarian Stimulation protocol Simple Cost Effective
Minimal side effects
Best success rates

29. TIME TO MOVE ON TO TOTAL GONADOTROPHIN CYCLE
Conclusion
Choice depends on doctors expertise and patient selection and choice
Gonadotrophin only protocol offers the best success rate
TIME TO MOVE ON TO TOTAL GONADOTROPHIN CYCLE

30. Thank you