Role of gonadotropins in iui
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Different protocols, indications, and monitoring of gonadotropins in IUI
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Role of gonadotropins in iui
- 1. Dr Antima Rathore Fellow – IHR, Guwahati 1
- 2. Physiology 2
- 3. HISTORY 3
- 4. Goal 4
- 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
- 30. Low dose step up 30
- 31. Conventional v/s Low dose Step-up Protocol 31Speroff, 8th edition, 2011
- 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
- 45. Miscarriage Rate • 20-25% • Advanced Maternal Age • Obesity • WHO II – elevated endogenous LH levels ↓ premature follicular luteinization 45
- 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
- 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
Editor's Notes
- Pregnant mare serum gonadotropin = equine corionic gonadotropin