1. Ovulation Induction Prof. Dr. Cem FICICIOGLU
Yeditepe University Hospital
Obstetrics and Gynecology

2. Foliculogenesis 60 days 14 days 14 days 1mm. 4-6 mm. 20 mm.
Gougeon, 1982

3. FSH Treshold FSH Ovulation Atresia Atresia
Baird DT: J Steroid Biochem 27: , 1987

4. Ovulation Induction alone, Prior to an IUI ( =< 2 follicles)
Prior to an IVF (>5 follicles)

5. Factors Demographical ( age, weight…..). Causes: OI+Coit IUI
IVF / ICSI.

6. Preparation Treatmen of the causes ( weight loses, PCO + Obesity )
BMI should be kg/m2
General health status ( anemia )
Folic support,
Spermiogram/HSG
Hormonal profile

7. Methods Hormonal Surgery Medical hmg CC/ Tamoxifen Ovarian drilling
Chemical
Surgery
Medical
hmg
CC/ Tamoxifen
Ovarian drilling
Weight loss
FSH (pure)
CC+Metformin
GnRH (puls)
Bromocriptin
Rec.FSH
Aromatase Inhibitors

8. Ovulation Problems Hipogonadotropik hipogonal anovulasyon ( %10 )
Group I
Hipogonadotropik hipogonal anovulasyon ( %10 )
Group II
Normogonadotropik normoöstrojenik anovulasyon-PCO (%70)
Group III
Hipergonadotropik hipoöstrojenik anovulasyon (%10)
Group IV
Hiperprolaktinemik anovulasyon (%10)

9. Group III Anovulation FSH , LH N, E2 Premature Ovarian Failure
Overian Resistans

10. Ovulation Follow up Methods
Old
Gynecologic Exam
Vaginal smear
Basal Body Temp
Progesterone
New
Basal body temp
Serial Ultrasonography
E2 levels
LH kit

11. Starting to the treatment
No ovarian cyts
Thin endometrium
ESTRADIOL <50 PG/ML
PROGESTERON <1.6 NG/ML

12. OI for IUI Aim Monofollicular development. Close up follow up.
Dosage should be adjusted based on response.

13. For < 4 folficular development
CC (clomiphene Citrate).
CC ± FSH veya ± HMG.
Aromatase Inhibitors
Gn. Standard step-up protokol.
Gn. Low dose step-up protokol.
Gn. Low dose step-up, step-down protokol.

14. Cycles Cancellation >3 Dominant Follicles
ESTRADİOL (E2 )>1500 PG/Ml
DOMİNANT Follicule ( - )

15. HCG timing Follicular diameter: 16-18mm
E pg/ml / per dominant foll.
Doz  IU
Early HCG -atresia, LUF
Late HCG -postmaturity

16. SERMs Binding to Er  ve Er  receptor Clomiphene Tamoxifen
Raloxiphene
Bazedoxifene

17. Clomiphene Citrate(CC)

18. CC 2 stereoisomer zu-clomiphene (38 %)(sis)
en-clomiphene (62 %)(trans),

19. En-clomiphene rapid degradation,
zu-clomiphene  long half life
Both isomere have estrogenic and antiestrogenic activity
Zu-clomiphene has much more estragenic activity

20. Absorbation GIS tract.

21. Anti-estrogenic activity
uterus
cervix
vagina

22.  FSH HYPOTALAMIC CC E2 RESEPTORS Endometrium and cervical (mukus)
Inhibition
OVERIAN STIMULATION

23. Hipotalamo-hipofizer aks sağlam olmalı!
CC - Endications
Normogonadotrophic, normoprolactinemic anovulation
PCOS - Anovulation
Unexplained Infertility
Prior IUI
Hipotalamo-hipofizer aks sağlam olmalı!

24. CC Contrendications E2< 40 pg/ml Liver dysfunction Pregnancy
Overian cyts
Age>35
FSH>11 IU

25. CC-Side effects CC- YAN ETKİLER % Hot flushes 11 Abdominal tenderness
Nausea/vomitting
Breast tenderness
Visual disturbance
Head ache
Hair loss
Dermatid, Depretion, % 11 7 2
1. 5
0.3

26. CC - Treatment Day 3-5. of the menstruel cycle, 50 mg/g; 5 days
Hiperresponders25 mg/g
No ovulation> 50 > 100 > 150 > 200 > 250 mg/g

27. When HCG
Follicular diameter 18-20mm,
34-40 hours laterovulation

28. Ovulation: USG Findings
Disappearnece of the follicles
Shrinkage of the follicles
Corpus Luteum
Fluids in the Douglas

29. Ovulation:Midluteal Progesterone
>= 5 ng/ml  ovulation
>= 9 ng/ml  pregnancy?

30. CC-Results Ovulation: %60-80 Pregnancy: %20-40 Multiple Pregnancy: %10
Abortion : %20

31. CC Failure 3 cycles, max dosage CC (150 mg) No ovulation
No pregnancy after successful 6 treatment cycles

32. CC Resistans Alternative Treatments
Weight loss (BMI)
İnsülin sensitizer agents + CC
(metformin 3x500mg, 2x850mg)
Corticosteroids (Deksametazon 0.5 mg/gün) + CC (DHEAS )
Prolaktin inhibating agent + CC
Aromatase inhibitors
Gonadotrophins + CC
Gonadotrophins
IUI + CC

33. Insulin Sensitisizer Drugs
Hiperinsulinemia
Folliküler gelişimin artan androjen düzeyi ile negatif etkilenmesi
CC cevabının bozulması

34. Metformin LH ve Androgens ↓ Glucose decreases Hepatic production ↓
Bowel Absorbtion ↓
LH ve Androgens ↓
Normal blood glucose does not decrease with Metformin

35. Metformin Side Effects
Anorexia,Nausea, Vomitting
Diarrheae, constipation,
Vit. B12 levels ↓
Aplastic anemia, Hemolitic anemia,
Trombositopenia, Agranülositosis
Laktic asidoz

36. Endometrial stimulation
Tamoxifen
HIPOTALAMIC
E2 RESEPTORS
TAMOXIFEN
 FSH
Endometrial stimulation
OVERIAN STIMULATION

37. Tamoxifen Pregancy rates looks like CC
Spontanous abortion rate  lower than CC
No side effect to the cervical mucus
Pts with breast cancer can use this for OI.

38. Aromatase Inhibitors
(AI)

39. Aromataz Aromatase, an enzyme Ovarium, Adipouse tissue, Muscles,
Liver,
Breast has Aromatase enzyme
Aromatase transforms androgens to estrogens (with FSH stimulation)

40. Androstenedion Testosteron Estron Estradiol
Aromatase
Aromatase
Estron
Estradiol

41. FSH    Overian Stimulation ANDROGENS AROMATASE ESTROGENS
HYPOTALAMUS
FSH   
Overian Stimulation

42. Aromatase Inhibitors Blocks the E2 reseptors (reversible)
No negative effects on Endometrium and Cervical muucus.
Multiple Pregnancy and OHSS risks are low

43. Aİ Generation Non-steroid Steroid (Non-reversibl) I Aminoglutetimid II
Roglitimid
Fadrozol
Formestan
III
Anastrozol
Letrozol
Vorozol
Eksemestan

44. Aromataz inhibition (%)AI
Dozage
Aromataz inhibition (%)
Anastrozol
Arimidex, 28 tb,
1 mg/g
97.3
Letrozol
Femara, 30 tb,
2.5 mg/g
>99.1

45. AI-Endications
CC resistans PCOS
Poor responders
Breast cancer

46. Hipersensitivity Aİ Contrendications Pregnancy Laktation
Renal insufficiency

47. Aİ - Dosage
2.5 – 5 (1-2 ) mg / day 3-7

48. AI Side effects Headache (6.9%) Nausea (6.3%), Periferal Edema (6.2%),
Fatigue (5.2%),
Hot flushes(5.2%),
Bone and back ache(4.8%),
Rash (3.4%)

49. ART Gonadotrophin Treatments WHO-Grup I WHO-Grup II
Normogonadotrophic patients
Hipogonadotrophic patients

50. Gonadotrophins CONTRENDICATIONS Overian Failure Hiperprolactinemia
No cooperation with patient

51. LOW-DOSE STEP-UP PROTOKOLÜ
100 IU/d
125 IU/d
75 IU/d
50 IU /d
35 günlük tedavi sonrası over cevabı olmazsa iptal

52. ***