Letrozole versus hMG in
intrauterine insemination cycles
H. Jamal; H. Serdaroglu; A. Baysoy;
E. Karatekeli; E. Attar; H. Ozornek
Istanbul, Turkey
Aromatase Inhibitors
i-Steroid group: Exemestane
ii-Non-Steroid imidazole group: Fadrozole.
iii-Non-Steroid triazole group: Anastrazole, letrozole
letrozole
letrozole
reversible
Increases endogenous
production of FSH
Suppressing estrogen
Enhances ovarian response
to gonadotropin stimulation
Increasing intraovarian
androgen levels
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
Indications
Breast cancer
Endometrial cancer
Endometriosis
uterine fibroids
Ovulation induction
a) Unexplained infertility
b) PCO
c) Poor responders
IUI
Human reproduction
Mitwally et al. 2003
Clinical pregnancy rate
25
20
15
10
19.1%
18.7%
10.5%
5
0
LetrozoleFSH
CC-FSH
FSH-only
IUI
Fertility and Sterility
Healey et al. 2003
Clinical pregnancy rate
25
20
15
20.9%
21.6%
FSH
FSH+Letrozole
10
5
0
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).
Letrozole group
IUI
hMG
group
80 couples
regular menstrual cycles
LETROZOLE GROUP(40 CASES)
primary infertility
hMG GROUP(40 CASES)
female age <36 years
All patients diagnosed as having unexplained infertility (lack of conception
after at least 2 year of regular unprotected intercourse)
• Transvaginal ultrasound
• Hormone profiles
• Semen analysis
• Hysterosalpingogram
• and/or Laparoscopy
normal
normal
OHSS and
multiple
pregnancy
length of
follicular phase
clinical
pregnancy rate
14 mm
follicles
premature
LH surge
endometrial
thickness
Letrozole
&
hMG
cost
LH surge?
LH-surge was defined as an
increase in LH level ≥100%
over mean of preceding two days.
Letrozole vs hMG
Day 3
HCG
Day 7
Letrozole 2x1
Day 3
Day 7
hMG 1x75ıu (<30 years)
hMG 1x150ıu(30years)
hMG
IUI was performed by the same physician for all patients.
No luteal support was given.
RESULTS
Letrozole
(n=40)
hMG
(n=40)
27.22±5.5
28.1±4.3
Duration of infertility (yrs)
5.3±2.1
5.9±3.2
baseline FSH (IU/l)
6.41±2.6
6.11±1.7
baseline LH (IU/l)
4.81±4.5
5.29±2.1
baselin E2 (pg/ml)
39.54±12.0
41.74±13.4
Age (yrs)
P: NS
RESULTS
Semen parameters before preparation for
insemination
Letrozole
hMG
[40]
[40]
Age of male partner (yrs)
31.43±4.1
30.10±5.9
Concentration
(x106/ml)
63.9 ± 41.3
66.3 ± 44.4
Motility (%)
59.7 ± 16.1
62.4 ± 15.3
NS
Normal sperm forms (%)
52.9 ± 11.3
54.1 ± 9.2
NS
P value
NS
NS
RESULTS
Letrozole
hMG
P value
12.77±1.9
11.90±1.7
NS
Follicle number
1.79±1.3
3.21±1.6
<0.001
Endometrial thickness(mm)
8.91±1.8
10.05±2.9
NS
93.3%
95.6%
NS
193.19±80
875.15±368
<0.001
2
2
NS
Follicular phase (days)
Trilaminar pattern
HCG day E2
Premature luteinization
RESULTS
Pregnancy rate
Multiple pregnancy
OHSS
Letrozole
hMG
P value
17.5%
15 %
NS
1(triplet)
1(twin)
NS
0
1(moderate)
NS
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.
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.
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.
Conclusion
• Despite significantly lower E2 levels in
the letrozole-treated women,
endometrial development was
unaffected, endometrial thickness and
pattern were similar in both groups.
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.
letrozole
efficient
cost effective
simple and
convenient
Thanks!