3. #
Faculty
• Dr. Sharda Jain
Prog. Director , Course Chairperson
• Dr Jyoti Agarwal
Director /Course Co- Chair person
• Dr. Aruna saxena
Director Course Co- Chairperson
• Dr. Jyoti Bhaskar
Director
• Dr. Abhishek Singh Parihar
Director
• Dr. Sushma Ved
Director
4. #
Rationale for COH in IUI
• Increasing the number of eggs available for
fertilisation
• Overcoming subtle defects in ovulatory
function and luteal phase.
5. #
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
6. #
Optimum Ovarian Stimulation
for IUI
2 – 3 follicles with Ø 18 – 20 mm.
Endometrium ≥ 8 mm thick & trilaminar.
IUI between Cycle D13 and D16, 36-40 hrs.
from HCG inj.
7. #
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
11. #
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
12. #
CC CHECK
Evaluation of the patient on Day 2
• Previous cycles
• TVS – ET , AFC and cysts
• Review reports of FSH, LH if available
13. #
CC FAILURE ( 40%)
No Pregnancy
3 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
CC FAILURE ( 40%)
No Pregnancy
3 CYCLES OF CC
WITH OVULATION AND TIMED INTERCOURSE
2 CYCLES OF CC WITH IUI2 CYCLES OF CC WITH IUI
14. #
CC RESISTANCE (20%)
3 CYCLES OF CC
NO OVULATION
CC RESISTANCE (20%)
3 CYCLES OF CC
NO OVULATION
CC + GONADOTROPHINS
LOD
CC + GONADOTROPHINS
LOD
GONADOTROPHINSGONADOTROPHINS
COST , PT’S CHOICE
COUNSELLING
Wt loss, extended CC,
adjuvants – metformin,
dexamethasone
15. #
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
Start early in cycle – Day 2 or Day 1
Add oestradiol valearate from day 8/9
Use all gonadotrophin cycle
16. #
TAMOXIFEN
• 20-40 mg/day D2- D7,max 60 mg/day
• Off label use for OI
• Ovulation rates- 65 to 75%
• Pregnancy rates- 30 to 35%.
• Advantage-
– No anti-estrogenic effect on endometrium.
– Improve bone density & lipid profile
• 2-3 times increased risk of endometrial Ca & DVT
• No evidence of a difference in effect between CC and
tamoxifen (Cochrane library, 2009)
21. #
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
22. #
2
3
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
8pmstat
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
24. #
CC - GONADOTROPINS
SEQUENCE
oCC in ovulatory disorders decreases the
total dose of gonadotropins used .
oConcurrent use of Gn allows follicular
development to desired extent.
oEndometrium is not adversely affected.
oOHSS is less common.
oCost is less.
25. #
Days 7 14 21 28
hCG
150IU 112.5IU 75IU hCG
Foll. ≥ 10 mm
75-150 U daily
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
2 6
26. #
EFFICACY OF
GONADOTROPINS
Low dose regimens result in:
• Monofollicular ovulation rate of- 70%.
• Pregnancy rate of -20%
• Multiple live birth rate of -5.7%
• Severe OHSS <1%
(all comparable with that of CC)
The duration of Gn therapy should not exceed 6
ovulatory cycles.
28. #
Advantages of Antagonist
Protocol
• Helps avoid IUI at weekends
• Prevents premature surge
• Compared to agonist – simple and
inexpensive
• Lower rates of OHSS
29. #
Laparoscopic Ovarian Drilling
• Main Indications
1. CC Resistance
2. Pts. who persistently hypersecrete LH
• Methods – Monopolar cautery or Laser
• Efficacy
50% of LOS treated Pts. adjuvant therapy will be reqd.
Addition of CC after 12 weeks if no ovulation detected
Addition of FSH should be considered after 6 months.
• Complications
Haemorrhage, bowel injury, adhesions, premature
menopause
30. #
MECHANISM OF ACTION
A.) Drilling of follicles releases androgen rich follicular fluid and
decreases androgen producing stroma.
B.) There is transient reduction in inhibin and precipitous fall in LH,
which increases secretion and expression of FSH.
C.) Crowding of cortex decreases which allows progress of normal
follicles to the surface resulting in resumption of normal ovulation.
LOD appears to be as effective as routine gonadotropin therapy
in the treatment of clomiphene-insensitive PCOS.
31. #
LAPAROSCOPIC OVARIAN
DRILLING (LOD)
Advantages
• High success rate
• Prolonged response
• ↓Multiple births
• ↓ OHSS
Disadvantages
• Adhesion formation
• Requires surgery
• 1/3 require ovulation
medications
• POF risk
• Less successful in
smokers 25% vs 95%
Technique: 4 puncture/ovary,4-5 mm
depth,40 watt coagulation for 4 sec
32. #
PATIENTS RESISTANT FOR LOS
• Increased duration of infertility (>3yr)
• Women with marked obesity, BMI>35kg/m2
• Increased free testosterone and free
androgen index
33. #
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.
34
The Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJThe Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
34. #
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 BJThe Cochrane Library 2011, Issue 6 Cantineau AEP, Cohlen BJ
35. #
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
36
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
36. #
• 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.
37
38. #
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
