1. Letrozole versus hMG in intrauterine insemination cycles
H. Jamal; H. Serdaroglu; A. Baysoy;
E. Karatekeli; E. Attar; H. Ozornek
Istanbul, Turkey

2. Aromatase Inhibitors i-Steroid group: Exemestane
ii-Non-Steroid imidazole group: Fadrozole.
iii-Non-Steroid triazole group: Anastrazole, letrozole

3. letrozole
letrozole
reversible

4. Increasing intraovarian
Increases endogenous
production of FSH
Enhances ovarian response to gonadotropin stimulation
Suppressing estrogen
Increasing intraovarian
androgen levels

5. Advantages of third-generation aromatase inhibitors
Extremely potent inhibition of aromatase
Very specific inhibition of aromatase without significant inhibition of other steroidogenesis enzymes Oral administration 100% bioavailability after oral administration Rapid clearance from the body (short half-life, ~ 45 hours)
No accumulation of the medications or their metabolites
No significant active metabolites Few mild adverse effects with high tolerability when given chronically Few contraindications or drug interactions Relatively inexpensive

6. Indications Breast cancer Endometrial cancer Endometriosis
uterine fibroids
a) Unexplained infertility
b) PCO
c) Poor responders
Ovulation induction

7. IUI Human reproduction Mitwally et al. 2003 Clinical pregnancy rate25 20 15
Clinical pregnancy rate
19.1% 10
18.7%
10.5% 5
FSH-only
Letrozole-
FSH
CC-FSH

8. IUI Fertility and Sterility Healey et al. 2003 Clinical pregnancy rate25 20 15
Clinical pregnancy rate
21.6%
20.9% 10 5
FSH
FSH+Letrozole

9. Objective
A prospective randomized study comparing the results of intrauterine insemination (IUI) in women undergoing ovulation induction with either letrozole or Human Menopausal Gonadotropin (hMG).

10. Letrozole group
IUI
hMG group

11. LETROZOLE GROUP(40 CASES)
80 couples
regular menstrual cycles
LETROZOLE GROUP(40 CASES)
primary infertility
female age <36 years
hMG GROUP(40 CASES)
All patients diagnosed as having unexplained infertility (lack of conception
after at least 2 year of regular unprotected intercourse)

12. Transvaginal ultrasound
Hormone profiles
Semen analysis
Hysterosalpingogram
and/or Laparoscopy
normal
normal

13. Letrozole & hMG OHSS and multiple pregnancy length of follicular phase
endometrial thickness
clinical pregnancy rate
Letrozole
&
hMG
14 mm follicles
cost
premature LH surge

14. LH-surge was defined as an over mean of preceding two days.
increase in LH level ≥100%
over mean of preceding two days.

15. Letrozole vs hMG Letrozole 2x1 hMG hMG 1x75ıu (<30 years)
Day Day 7
Day Day 7
HCG
Letrozole 2x1
hMG 1x75ıu (<30 years)
hMG
hMG 1x150ıu(30years)

16. IUI was performed by the same physician for all patients.
No luteal support was given.

17. RESULTS hMG Letrozole (n=40) (n=40) Age (yrs)
Duration of infertility (yrs)
baseline FSH (IU/l)
baseline LH (IU/l)
baselin E2 (pg/ml)
Letrozole
(n=40)
27.22±5.5
5.3±2.1
6.41±2.6
4.81±4.5
39.54±12.0
hMG
(n=40)
28.1±4.3
5.9±3.2
6.11±1.7
5.29±2.1
41.74±13.4
P: NS

18. Semen parameters before preparation for insemination
RESULTS
Semen parameters before preparation for insemination
Letrozole
[40]
31.43±4.1
63.9 ± 41.3
59.7 ± 16.1
52.9 ± 11.3
hMG
[40]
30.10±5.9
66.3 ± 44.4
62.4 ± 15.3
54.1 ± 9.2
P value NS
Age of male partner (yrs)
Concentration
(x106/ml)
Motility (%)
Normal sperm forms (%)

19. RESULTS hMG Letrozole 11.90±1.7 12.77±1.9 NS 3.21±1.6 1.79±1.3
10.05±2.9
95.6%
875.15±368 2
Letrozole
12.77±1.9
1.79±1.3
8.91±1.8
93.3%
193.19±80 2
P value NS
<0.001
Follicular phase (days)
Follicle number
Endometrial thickness(mm)
Trilaminar pattern
HCG day E2
Premature luteinization

20. RESULTS hMG 15 % 1(twin) 1(moderate) P value NS Letrozole 17.5%
1(triplet)
Pregnancy rate
Multiple pregnancy
OHSS

21. The mean dose of hMG (mean number of ampoules/cycle) was 15
The mean dose of hMG (mean number of ampoules/cycle) was 15.5 ampoules/cycle. While the dose of letrozole were stable (10 tablets/cycle).
Letrozole had a cost of 43 $ per cycle while hMG was more costly with 225 $ per cycle.

22. Conclusion
Although low estradiol levels and less number of mature follicles were obtained at the time of the hCG in the letrozole group, pregnancy rates were similar in both groups.

23. Conclusion
Another outcome we noticed that the stimulation time lasted longer in the letrozole group. As other authors cited before that this longer time of stimulation may have beneficial effects on oocyte maturation and oocyte quality and this is maybe a reason that more pregnancies occured in the letrozole group.
Use of Neuroanatomy has been one of the most venerable methods of identifying the location of damage and it’s out come -
Gall & phrenology
Staining uses brains preserved in formalin - and stained using an enzyme
Useful for identifying functional connections
Neuroanatomy essentially divided into 2 areas -
Gross neuroanatomy - (eg Brodmann)
Fine neuorantomy (eg histology)
Neurophysiology
Electrical stimulation (eg Penfield)
Single cell recordings
Lesions (eg Experimental Ablation)

24. Conclusion
Despite significantly lower E2 levels in the letrozole-treated women, endometrial development was unaffected, endometrial thickness and pattern were similar in both groups.

25. Conclusion
Serious complications (OHSS, multiple pregnancy) were rare in the two groups. Low estradiol levels and less number of mature follicles at the time of the hCG in the letrozole group may be a reason to minimize and thereby avoid the complications of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. But to compare such an outcome, a large study including a very large number of patients must be required.

26. letrozole
efficient
cost effective
simple and convenient

27. Thanks!