Different protocols, indications, and monitoring of gonadotropins in IUI

1. Dr Antima Rathore
Fellow – IHR, Guwahati 1

2. Physiology
2

3. HISTORY
3

4. Goal
4

5. Benefits
Higher
Pregnancy
Rates
5

6. Drawbacks
6
Costly
Multiple Gestation
OHSS

7. Objective Of Ovulation Induction
Monofollicular development
7

8. Gonadotropin Preparations
FSH Only
LH Only
Both FSH + LH
8

9. 9

10. Human Menopausal Gonadotropins
(menotropins)
hMG
• Source - urine of postmenopausal women
• Varying amounts of hCG & urinary protiens
10
75 IU FSH
+
75 IU LH

11. Urofollitropin or Purified Urinary FSH
• LH removed with polyclonal antibodies
• Still contain high amount of urinary protein
11
FSH
75 IU
LH
< 1 IU

12. Highly Purified FSH (HP-FSH)
• Use of highly specified monoclonal antibody
extract FSH
12
FSH
75 IU
LH
< 0.1 IU
Protein
< 5%
less than 0.001 IU LH

13. 13

14. Recombinant Gonadotropins
• Genetic Engineering
• Absent Urinary Protein
• More Consistent Supply
• Less batch-to-batch
variation in biologic
activity
14

15. Differences between hMG and
FSH formulations
15

16. 16

17. Indications
1. Hypogonadotropic
Hypogonadism
2. Clomiphene-Resistant
Anovulation
3. Unexplained Infertility
4. Elderly Patients
17

18. Hypogonadotropic Hypogonadism
(WHO Group I)
Drug Of Choice
↓
Gonadotropins
containing
both FSH and LH
18
↓FSH
↓LH

19. Clomiphene-Resistant Anovulation
(PCOS; WHO Group II)
• Purified FSH preparations
offer a theoretical advantage
• However - there is no
evidence that purified FSH
has greater efficacy than
hMG and either may be used
19

20. Clomiphene-Resistant Anovulation
(PCOS; WHO Group II)
20

21. Switch from CC to gonadotropins
21

22. Efficacy
22

23. Unexplained Infertility/Elderly Patient
+
Increase Cycle Fecundity
23
SUPEROVULATI
ON
IUI

24. Huttenen et al (1999)
24

25. 25

26. Protocols
ALONE
Or
In combination with oral ovulogens
26

27. Protocols
I. Step-up
1.
Conventional=Stand
ard
2. Low dose
II. Step-down
III. Chronic low dose
27

28. “Step-up” Protocols
• Mimick natural progression of gonadotropin
• Starting dose
– Conventional – 150 IU
– Low Dose Step-up – 75 IU
28

29. Conventional “Step-up” Protocol
29
D
4

30. Low dose step up
30

31. Conventional v/s Low dose Step-up
Protocol
31Speroff, 8th edition, 2011

32. Step-down Protocol
32

33. Chronic low-dose
• Starting dose - 37.5-75 IU
• Duration of starting dose - 14 days
• Monitoring – TVS (every 7th day)
• Weekly dose increment - 37.5 IU (till one dominant follicle
seen)
White et al. J Clin Endocrinol Metab
1996;81:3821–4
33

34. Chronic low-dose
• Suitable for PCOS
• Less chances of OHSS
• Take time
• Increases cost of treatment
34

35. Fixed dose regimen
Gonadotropin dose
Constant
throughout the stimulation
35

36. Sequential CC/gonadotropin Protocol
36
1 2 3 4 5 6
Clomiphene Citrate
Start
7
TVS
8 9

37. Sequential CC/gonadotropin Protocol
(of gonadotropin therapy)
↓
Decreased by 50%
Cycle fecundity - Similar to gonadotropins alone
37
Dose
Duration
Cost

38. Reversed hMG/CC Protocol
38
1 2 3 4 5 6
Clomiphene
Citrate
50 mg
Till Ovulation
Start
7
First 4 days
8 9

39. Reversed hMG/CC Protocol
• Good responders
– young women
– unexplained infertility
– mild male factor
• PCOS
• Avoid the risk of severe OHSS
• Simple, Safe, Cost Effective
39

40. 40

41. Complications
• OHSS - Life threatening
 Risk factors
– young age
– low body weight
– PCOS
– higher doses of gonadotropins
– previous episodes of hyperstimulation
– hCG – trigger & luteal phase support
41

42. Risk of OHSS
E2 peak (pg/ml)
(Speroff et al, 2006) 42

43. Risk of OHSS
1) Macklon et al, 1999
2) Kamrava et al., 1982; Hugues et al., 2006
3) Speroff 2006
43
>3 follicles
16 mm
> 4 follicles
≥ 14 mm
Stop stimulation & withhold hCG

44. Congenital anomalies
44
No increase

45. Miscarriage Rate
• 20-25%
• Advanced Maternal Age
• Obesity
• WHO II
– elevated endogenous LH levels
↓
premature follicular luteinization
45

46. Recommendations
46

47. Speroff 8TH Edition, 2011
“….exogenous gonadotropins should be
used only by clinicians having the
training and experience necessary to
provide safe and effective treatment.”
47

48. Take home message
48

49. 49

50. Contraindications
Rare
1.Hypersensitivity to Gnt or to any of the excipients
2. Ovarian, uterine, or breast cancers
3. Tumors of the hypothalamus & pituitary gland
4. Ovarian enlargement or cyst not due to PCOS
5.Lactation
6. AUB
50