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IUI indications, Ovarian stimulation protocols CC, aromatase inhibitors, gonadotropins

IUI indications, Ovarian stimulation protocols CC, aromatase inhibitors, gonadotropins. Hakan Özörnek, MD EUROFERTIL İstanbul. Indications. Male subfertility Unexplained infertility Endometriosis (mild) Cervical factor Ejaculatory dysfunction Immunologic infertility. Contrindications .

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IUI indications, Ovarian stimulation protocols CC, aromatase inhibitors, gonadotropins

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  1. IUI indications, Ovarian stimulation protocols CC, aromatase inhibitors, gonadotropins Hakan Özörnek, MD EUROFERTIL İstanbul

  2. Indications • Male subfertility • Unexplained infertility • Endometriosis (mild) • Cervical factor • Ejaculatory dysfunction • Immunologic infertility

  3. Contrindications • Tubal infertility • Severe male infertility • Severe endometriosis • Decreased ovarian reserv • Age > 40

  4. ART in Europe, 2006: results generated from European registers by ESHREJ. de Mouzon*, V. Goossens, S. Bhattacharya, J.A. Castilla, A.P. Ferraretti, V. Korsak, M. Kupka, K.G. Nygren, A. Nyboe Andersenand The European IVF-monitoring (EIM) Consortium, for the (ESHRE)

  5. ÜYTE yönetmeliği MADDE 18 – (8) İstenmeyen durum olan, anne ve çocuk sağlığını riske eden çoğul gebeliklerin önlenmesi esastır. Bu kapsamda; a) ÜYTE yöntemlerinden biri olan klasik ovulasyon indiksiyonu ile 2 (iki) den fazla folikül gelişmemesi hedeflenmelidir. Çoğul gebeliklerin önlenmesi için üç veya daha fazla folikül gelişmesi halinde artifisyel inseminasyon işlemi yapılması yasaktır.

  6. Male subfertility

  7. Unexplained subfertility

  8. Cervical factor

  9. CC/Letrazol protocol E2 control LH control Ovulation induction

  10. Gonadotropin protocol E2 control LH control 50-75 IU/day Ovulation induction

  11. Advantages of oral drugs • Low incidence of multiple pregnancies • Low incidence of OHSS • Low cost • Less need for cycle monitoring • More comfortable

  12. CC • Competitive antagonist of ovarian estrogen • Requires an intact hypothalamic-pituitary-ovarian axis and serum estradiol > 50 pg/ml. • Endometrial thickness is initially decreased, but is later increased compared to natural cycles as rising estrogen concentration overcomes the antiestrogen effect. [Randall JM, F&S, 1991]

  13. Letrazol • Third generation aromatase inhibitor • Act directly to the ovary to decrease production of estrogen • Intraovarian androgens accumulate mid sized follicles become atretic • Multiple follicular ovulation are reduced compared to CC • Used «off label»

  14. CC IUI Dickey RP, et al., Fertil Steril, 2002

  15. CC IUI Dickey RP, et al., Fertil Steril, 2002

  16. CC IUI Dickey RP, et al., Fertil Steril, 2002

  17. CC IUI Dickey RP, et al., Fertil Steril, 2002

  18. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  19. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  20. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  21. CC for unexplained subfertility in women Objectives Clomiphene citrate in improving pregnancy outcomes in women with unexplained subfertility, dose range of 50 to 250 mg for up to 10 days. The primary outcome was live births. Selection criteria Only randomised controlled trials were included. Data collection and analysis Seven trials were included in this review. Hughes E, et al., Cochrane Database of Systematic Reviews 2010

  22. CC for unexplained subfertility in women Main results 1159 participants from seven trials were collated. There was no evidence that CC was more effective than no treatment or placebo for live birth (odds ratio (OR) 0.79, 95% CI 0.45 to 1.38; P = 0.41) or for clinical pregnancy per woman with intrauterine insemination (IUI) (OR 2.40, 95% CI 0.70 to 8.19; P = 0.16). Authors' conclusions There is no evidence of clinical benefit of clomiphene citrate for unexplained fertility. . Hughes E, et al., Cochrane Database of Systematic Reviews 2010

  23. Clomiphene citrate or aromatase inhibitors forsuperovulation in women with unexplained infertilityundergoing intrauterine insemination: a prospective randomized trialAhmed Badawy, et al., Fertil Steril, 2009

  24. Letrazol vs CC • Ameta-analysis of four published randomized controlled trials for ovulation induction in a total 662 patients with PCOS now provides strong evidence that letrozole is at least as effective as CC, the present gold standard, for ovulation induction with similar pregnancy rates ([RR] 1.02; 95% CI0.83, 1.26). • Letrazole is equally effective in inducing ovulation, but without antiestrogenic adverse effects, as a first-line therapy. Casper RF, Fertil &Steril, 2009

  25. Letrazol vs CC • 5 fertility centers in Canada. • 911 newborns from women who conceived following CC or letrozole treatment. • Congenitalmalformations and chromosomal abnormalities in the letrozole group 2.4% and in the CC group 4.8%. • The major malformation rate in the letrozole group was 1.2%and in the CC group was 3.0%. Tulandi T, et al. Fertil Steril, 2006

  26. Gonadotropins IUI Dickey RP, et al., Fertil Steril, 2002

  27. Gonadotropins IUI Dickey RP, et al., Fertil Steril, 2002

  28. Gonadotropins IUI Dickey RP, et al., Fertil Steril, 2002

  29. Gonadotropins IUI Dickey RP, et al., Fertil Steril, 2002

  30. Gonadotropins IUI Dickey RP, et al., Fertil Steril, 2002

  31. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  32. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  33. Cumulative pregnancy rate Dickey RP, et al., Fertil Steril, 2002

  34. Effect of age Dickey RP, et al., Fertil Steril, 2001

  35. Pregnancy rates following IUI Cantineau et al., Cochrane, 2007

  36. Letrazol vs FSH Baysoy A, et al. RBM Online, 2006

  37. Letrazol vs FSH Baysoy A, et al. RBM Online, 2006

  38. Letrazol vs FSH Odysseas, et al., Fertil Steril, 2008

  39. Pregnancy rate FSH vs FSH+Letrazol Requena, et al. Hum Reprod Update, 2008

  40. CC-FSH vs FSH alone vs Letrazol Ganesh, et al. J Assist Reprod Genet, 2009

  41. CC-FSH vs FSH alone vs Letrazol Ganesh, et al. J Assist Reprod Genet, 2009

  42. Premature LH surge during mild FSH stimulation (203 cycles) Lambalk et al., Hum Reprod,2006

  43. OPR with or without antagonist

  44. A randomized clinical trial to evaluate optimaltreatment for unexplained infertility: the fast track and standard treatment (FASTT) trialRichard H. Reindollar, et al FS 2010 • 3 x CC/IUI + 3 x FSH/IUI + 6 x IVF (n=247) • 3 x CC/IUI + 6 x IVF (n=256)

  45. A randomized clinical trial to evaluate optimaltreatment for unexplained infertility: the fast track and standard treatment (FASTT) trialRichard H. Reindollar, et al FS 2010

  46. A randomized clinical trial to evaluate optimaltreatment for unexplained infertility: the fast track and standard treatment (FASTT) trialRichard H. Reindollar, et al FS 2010

  47. A randomized clinical trial to evaluate optimaltreatment for unexplained infertility: the fast track and standard treatment (FASTT) trialRichard H. Reindollar, et al FS 2010

  48. Conclusion • IUI is the first choise particularly in male subfertility and unexplained infertility • Letrazol is as effective and safe as CC. Absence of antiöstrogenic effect of Letrazol is an advantage • Adding of oral drugs to gonadotropins reduce the cost of the therapy but the pregnancy rate is not differ • In a subgroup of patients whose basal E2 < 30 pg/ml is gonadotropins preferable • Adding GnRH antagonist to a gonadotropin stimulation bevor IUI increase the pregnancy rates • Due to new regulation of ministery of health oral drugs are more cost effective than the gonadotropins

  49. F A K A T !!!

  50. Thank you

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