Significant increase in live birth rate is found when IUI is done with stimulation compared with IUI in natural cycle in women with Unexplained Infertility .

1. Ovulation
Ovulation
Induction & IUI
Induction & IUI
DR NABANEETA PADHY
DR NABANEETA PADHY
MEDICAL DIRECTOR
MEDICAL DIRECTOR
FEMELIFE FERTILITY FOUNDATION
FEMELIFE FERTILITY FOUNDATION
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2. Significant increase in live birth rate
was found when hyperstimulation was
compared with IUI in natural cycle in
women with Unexplained Infertility
Cochrane Systematic review 2008 ; issue 2
However concern about multiple pregnancy and
OHSS remains

3. IUI with controlled OH significantly
improved the probability of conception in
subfertility in men
Conchrane database Syst Rev . 2007
However in case of severe semen defect ( with < 1
million motile sperm after semen preparation ) IUI in
natural cycle should be the treatment of choice.

4. To Whom ?
What ?
When ?
How ?

5. To Whom ?

6. Absent Ovulation
Infrequent Ovulation
Inadequate FSH stimulation
Inadequate corpus luteum function
PCO
Unexplained infertility
To time the Ovulation
To increase the number of oocytes
IVF / ICSI

7. Every lady entering in Infertility centre receives ….

8. INDUCTION OFINDUCTION OF
OVULATIONOVULATION
** ANOVULATORY CYCLESANOVULATORY CYCLES
* DYSOVULATORY CYCLES* DYSOVULATORY CYCLES
* NORMAL OVULATORY CYCLES* NORMAL OVULATORY CYCLES

9. When ?
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10. It takes about 10 wks for the primordial follicle to
develop into preantral stage, which is then capable of
gonadotropic responsiveness .
(gonadotropic independent folliculogenesis )
A cohort of these preantral follicles start growing
due to rising FSH. One of them becomes the dominant
follicle (by day 6) which in turn by producing increasing
amount of estrogen, decreases FSH production through
negative feedback causing atresia of less developed
follicles.

11. Dominent
follicle

12. The role of ovulation inducing agents -The role of ovulation inducing agents -
to disturb this normal relationship byto disturb this normal relationship by
increasing the FSH above threshold whichincreasing the FSH above threshold which
will rescue a follicular cohortwill rescue a follicular cohort
( before they undergo atresia)( before they undergo atresia)
Hence more number of follicles will reach toHence more number of follicles will reach to
the preovulatory stage.the preovulatory stage.

13. Rescued
Dominant
← drug

14. How much ?

15. * Age* Age
* Weight* Weight
* Day 2 FSH* Day 2 FSH
* Ovarian volume & Antral follicle index* Ovarian volume & Antral follicle index

16. What ?

17. Clomiphene Citrate :Clomiphene Citrate :
selective estrogen receptor modulatorselective estrogen receptor modulator

18. * 75 % of conceptions occur during first
three cycles . When no pregnancy is achieved
within 6 treatment cycles alternative therapy
should be chosen.
* Clomiphene should be used for maximum of
12 months in patient’s life time and for a
maximum of 6 months consequently.

19. * Dose more than 150 mg leads to
hypoestrogenic effect on endometrium.
* CC does not appear to increase the chances
of pregnancy in women who ovulate regularly
but failed to conceive after 1 year of
unprotected sex.

20. Drawbacks :
Despite high ovulation rate, low pregnancy rate
1.Multiple pregnancy : 10 %
2.Antiestrogenic – detrimental to sperm
transport and embryo implantation.
3.Sometimes risk of OHSS

21. 5.The effect lasts longer , may be for weeks even
with a single dose of 50 mg. Its presence at the
time of ovulation inhibits progesterone formation
by granulosa cells in luteal phase
6.Can give premature LH surge due toCan give premature LH surge due to
supraphysiological estradiol levelssupraphysiological estradiol levels
7. Cannot be used in patients with
hypogonadotropic dysfunction

22. In search of better drug with improved
pregnancy rate , reduction in the incidence
of multiple pregnancy rate & ……

23. Failure with or Resistance to
CC

24. Alternative / Adjuvant
Treatment for CC
Cochrane review 2005 Jan
Included 12 RCTs

25. * Tamoxifen
* Dexamethasone
* Bromocreptine
* Aromatase Inhibitor
* Insulin Sensitisers
* Oral Contraceptive Pretreatment
* Gonadotropins

26. * CC + Dexamethasone resulted in
significant improvement in PR in CC
resistance cases.
* Significant increase in PR in CC cycles
when pretreatment with oral contraceptives
than CC alone in PCOS

27. * Tamoxifen
* Dexamethasone
* Bromocreptine
* Oral Contraceptive Pretreatment
* Aromatase Inhibitor
* Insulin Sensitisers
* Gonadotropins

28. LetrozoleLetrozole
non steroidal selective estrogennon steroidal selective estrogen
enzyme modulatorenzyme modulator

29. In last few years , it has added another
option for the ovarian stimulation

30. First report by Casper and Mitwaly group in
2001 , saying ,
“ Preliminary evidence suggest that AI
may replace CC in future because of
similar efficacy and less side effects. ”

31. Aromase Inhibitor Treatment

32. * Inhibition of estrogen synthesis by
aromatase inhibition - release estrogenic
negative feedback
(Mitwally and Casper 2001)
* Accumulation of androgens locally
may increase follicular sensitivity to
FSH
(Vendola et al 1998)

33. Clomiphene Vs Letrozole

34. Results
1.CC is superior to AI as first line of
treatment
2.Both have equal results as far as
ovulation rate, and pregnancy rates are
concerned
3.Letrozole can replace CC as first line of
treatment

35. Why
to
prefer
?

36. *Short half life
* Implantation rates improve with the
reduction of supra-physiologic level of
estrogen associated with COH,which is
believed to have deleterious effects on the
embryos or the endometrium
* Reduction of estrogen levels during
induction cycles may prevent a premature
surge of LH

37. * Letrozole is safe, convenient, inexpensive
and has the potential to replace Clomiphene
as the first line of choice for OI, especially
when it has to be used along with
gonadotropins
* Letrozole used with sequential FSH
administration significantly reduces the FSH
dose for COH & hence becomes cost
effective therapy

38. * Improvement is seen in ovarian
response to FSH in poor responders

39. * Tamoxifen
* Dexamethasone
* Bromocriptine
* Aromatase Inhibitor
* Gonadotropins
* Insulin Sensitisers
* Oral Contraceptive Pretreatment

40. When to use
gonadotropins ?

41. Failure with
or Resistance
to Oral OI
drugs

42. On evaluating effectiveness of IUI ,
pregnancy rates are significantly
higher in women who received
gonadotropins
Hughes 1997, Cohlen 1998 , Guzick et al 1998

43. Reducing the dose of
gonadotropins without
compromising pregnancy rate
would definitely reduce the overall
costs & possibly improve the cost
effectiveness of IUI treatment

44. Stimulating endogenous
gonadotropin production with
sequential use of lower doses of
exogenous FSH for COH
Mitally &
Casper

45. MultiplePregnancyRate
MultiplePregnancyRate
Mitwallyetal,AJOG2005;192(2):381-6
Mitwallyetal,AJOG2005;192(2):381-6
0
5
10
15
20
25
CC
CC
FSH
Le
Let
2.5
Letr
5mg
Percent

46. Adjunctive Therapy with FSH in poor
responders
Mitwaly and Casper (2001) examined the use of
Letrozole with FSH for poor responders
undergoing ovarian superovulation and IUI
Letrozole 2.5 mg/day from Day 3 to Day 7 was
used with FSH(50-225 IU starting on day 7)
* Significant reduction in the FSH dose
* An improvement in ovarian response to FSH

47. Comparison of daily and alternate day
rFSH stimulation protocols for IUI
Tulandi T ,et al Fertil Steril 2008 March
* Total dose needed was greater in daily
injection group
* CPR was 42% in daily inj group
Vs
19% in alternate –day group

48. * Tamoxifen
* Dexamethasone
* Bromocreptine
* Aromatase Inhibitor
* Gonadotropins
* Insulin Sensitisers
* Oral Contraceptive Pretreatment

49. The recognition that Insulin Resistance has
a pivotal role in the pathogenesis of PCOS
revolutionalized our understanding of this
complex disorder

50. Metformin combined with CC is more effective
in ovulation induction as compared with CC
alone especially in obese PCOS
Cochrane review
Jan 2008
However , the optimal duration for metformin
treatment before initiation of CC is unknown as
in Cochrane review they could not find any data
over short term Vs long term metformin
pretreatment.

51. Use of Metformin in PCOS : Metanalysis
Metformin alone, CC alone & Met + CC
Outcomes : Ovulation rate , PR & LBR
Conclusion :
1.Metformin improved the odds of ovulation in women
with PCOS when compared to placebo
2.When combined , there is increase in ovulation & PR
especially in obese PCOS & CC resistance cases.

52. EBM :
1.There is evidence that metformin is effective in
restoring ovulation in anovulatory cycles with
PCOS
2. It is more cheaper option than laparoscopic
ovarian drilling as the second therapeutic step
in PCOS with CC resistance
3. Coadministration of metformin can prevent
hyperstimulation in PCOS on treatment with
gonadotropins in IVF cycles

53. GnRH Antagonist in IUI

54. * In cases of premature LH surge
* To time weekend IUI

56. Ovurelix
0.25 mg/day is given from the day when
follicle reaches to size of 14 -15 mm till
hCG administration

57. Conclusion

58. 1.CC was the first line of treatment for OI
for many decades.
2.In CC resistance cases , Metformin + CC
& Dex + CC has shown significant
improvement in PR and got upper hand
in treatment of CC resistance over
laparoscopic drilling
3.AI have the potential to replace CC as the
first line of treatment with its several
advantages

59. 4. Addition of low dose gonadotropins to oral
ovulogens significantly improves PR in IUI
5. Letrozole is superior to CC whenever
gonadotropins have to be added
6. There is no role of Bromocriptin in CC
resistance cases with normal prolactin levels
7. Pretreatment with OC pills is useful
8. Tamoxifen and CC has comparable results but
combination of two does not improve PR

60. 9. GnRH Antagonist is of great value in
cases of premature LH surge.

61. Case 1
26 yrs old, married for 3 yrs, laparoscopy done , Found to
be PCOS. Drilling done , semen analysis shows count 10
million with rapid motility 10%
What next- IUI or not

62. Case 2
25 yrs old female , primary infertility ,prolactin level is 56
pg/ml
How to manage
Start bromocriptine/ pergolides or not

63. Case 3
Day 3 LH for a 25 yr old is 7 IU
Drugs to be used for ovulation
induction ?

64. Case 4
Young couple , patent tubes, male factor
normal, ovulation induction and IUI done
for 3 cycles , failed
What next ?

65. Case 5
Young couple , h/o ectopic pregnancy
twice affecting both tubes, but managed
medically. Recent HSG shows bilateral
patent tubes
Shall we proceed for IUI ?

66. Case 6
38 yr old lady recently married , asking for IUI
HOW TO COUNSEL ?

67. THANKYOU
THANKYOU
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