letrozole versus hmg in intrauterine insemination cycles h. jamal; h. serdaroglu; a. baysoy; e....
TRANSCRIPT
Letrozole versus hMG in Letrozole versus hMG in intrauterine insemination cyclesintrauterine insemination cycles
HH.. Jamal; Jamal; H. H. Serdaroglu; Serdaroglu; A. A.
Baysoy; Baysoy; E. E. KaKaratekelratekelii;; E. E. Attar; Attar; H. H.
OzornekOzornek
Istanbul, TurkeyIstanbul, Turkey
Aromatase Inhibitors
iii-Non-Steroid triazole group: Anastrazole, letrozole
i-Steroid group: Exemestane
ii-Non-Steroid imidazole group: Fadrozole.
letrozole
letrozole
reversible
Enhances ovarian response to gonadotropin stimulation
Increases endogenous
production of FSH
Increasing intraovarian androgen levels
Suppressing estrogen
Advantages of third-generation aromatase inhibitors
Extremely potent inhibition of aromataseVery 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 metabolitesNo significant active metabolites
Few mild adverse effects with high tolerability when given chronically
Few contraindications or drug interactions
Relatively inexpensive
IndicationsIndications
Ovulation induction
Breast cancer
Endometrial cancer
Endometriosis
uterine fibroids
a) Unexplained infertility
b) PCO
c) Poor responders
Cli
nica
l pre
gnan
cy r
ate
Human reproductionMitwally et al. 2003
0
5
10
15
20
25
Letrozole-FSH
CC-FSH FSH-only
IUI
19.1%18.7%
10.5%
Cli
nica
l pre
gnan
cy r
ate
Fertility and SterilityHealey et al. 2003
0
5
10
15
20
25
FSH FSH+Letrozole
IUI
20.9% 21.6%
A prospective randomized study comparing the results of intrauterine insemination (IUI) in women undergoing ovulation induction with either letrozole or Human Menopausal Gonadotropin (hMG).
ObjectiveObjective
Letrozole group
hMG group
IUI
80 couples
LETROZOLE GROUP(40 CASES)
hMG GROUP(40 CASES)
regular menstrual cycles
primary infertility
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
length of follicular phase endometrial
thickness
cost
premature LH
surge
14 mm follicles
clinical pregnancy rate
OHSS and multiple
pregnancy
Letrozole&
hMG
LH-surge was defined as an LH-surge was defined as an increase in LH level ≥increase in LH level ≥10100% 0%
over mean of preceding two days.over mean of preceding two days.
LH surge?
LetrozoleLetrozole vvs s hMGhMG
Day 3 Day 7
Day 3 Day 7
Letrozole 2x1
hMGhMG 1x75ıu (<30 years)
hMG 1x150ıu(30years)
HCGHCG
No luteal support was given.
IUI was performed by the same physician for all patients.
RESULTSRESULTS
Age (yrs)Age (yrs)
Duration of infertility (yrs)Duration of infertility (yrs)
baselinebaseline FSH (IU/l) FSH (IU/l)
baselinebaseline LH (IU/l) LH (IU/l)
baselinbaselin E E2 2 (pg/ml)(pg/ml)
LetrozoleLetrozole(n=(n=440)0)
2277.22±.22±55.5.5
55.3±.3±22.1.1
66.41±2.6.41±2.6
44.81±.81±44.5.5
39.54±139.54±12.2.00
hMGhMG(n=(n=4040))
28.1±4.328.1±4.3
55.9±.9±33.2.2
66.11±.11±11..77
5.29±5.29±22..11
441.74±1.74±1313.4.4
P: NSP: NS
LetrozoleLetrozole
[[4040]]
31.43±4.131.43±4.1
663.93.9 ± ± 41.3 41.3
59.759.7 ± ± 116.16.1
5522.9.9 ± ± 11.311.3
Semen parameters before preparation for insemination
RESULTSRESULTS
Age of male partner (yrs)Age of male partner (yrs)
ConcentrationConcentration
((xx101066/ml)/ml)
MMotility (%)otility (%)
Normal sperm forms (%)Normal sperm forms (%)
P valueP value
NSNS
NSNS
NSNS
NSNS
hMGhMG
[[4040]]
30.10±30.10±55.9.9
66.366.3 ± ± 44.444.4
662.42.4 ± 1 ± 15.35.3
54.154.1 ± ± 9.9.22
LetrozoleLetrozole
1122.77±.77±11..99
11.79±1.3.79±1.3
8.8.991±1±11.8.8
93.3%93.3%
1193.19±893.19±800
22
hMGhMG
1111..9090±±11.7.7
3.21±1.63.21±1.6
1010.05±.05±22..99
95.6%95.6%
875.15±3875.15±36868
22
Follicular Follicular pphasehase (days(days))
Follicle numberFollicle number
Endometrial Endometrial tthicknesshickness(mm)(mm)
Trilaminar patternTrilaminar pattern
HCG day E2HCG day E2
Premature luteinizationPremature luteinization
RESULTSRESULTS
P valueP value
NSNS
<<0.0010.001
NSNS
NSNS
<0.001<0.001
NSNS
LetrozoleLetrozole
17.5%17.5%
1(triplet)1(triplet)
00
hMGhMG
15 %15 %
1(twin)1(twin)
1(moderate1(moderate))
Pregnancy ratePregnancy rate
Multiple Multiple pregnancypregnancy
OHSSOHSS
RESULTSRESULTS
P P valuevalue
NSNS
NSNS
NSNS
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!