4 Increasing intraovarian Increases endogenousproduction of FSHEnhances ovarian response to gonadotropin stimulationSuppressing estrogenIncreasing intraovarianandrogen levels
5 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
6 Indications Breast cancer Endometrial cancer Endometriosis uterine fibroidsa) Unexplained infertilityb) PCOc) Poor respondersOvulation induction
7 IUI Human reproduction Mitwally et al. 2003 Clinical pregnancy rate 252015Clinical pregnancy rate19.1%1018.7%10.5%5FSH-onlyLetrozole-FSHCC-FSH
8 IUI Fertility and Sterility Healey et al. 2003 Clinical pregnancy rate 252015Clinical pregnancy rate21.6%20.9%105FSHFSH+Letrozole
9 ObjectiveA prospective randomized study comparing the results of intrauterine insemination (IUI) in women undergoing ovulation induction with either letrozole or Human Menopausal Gonadotropin (hMG).
11 LETROZOLE GROUP(40 CASES) 80 couplesregular menstrual cyclesLETROZOLE GROUP(40 CASES)primary infertilityfemale age <36 yearshMG GROUP(40 CASES)All patients diagnosed as having unexplained infertility (lack of conceptionafter at least 2 year of regular unprotected intercourse)
13 Letrozole & hMG OHSS and multiple pregnancy length of follicular phase endometrial thicknessclinical pregnancy rateLetrozole&hMG14 mm folliclescostpremature 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 7Day Day 7HCGLetrozole 2x1hMG 1x75ıu (<30 years)hMGhMG 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±5.55.3±2.16.41±2.64.81±4.539.54±12.0hMG(n=40)28.1±4.35.9±3.26.11±1.75.29±2.141.74±13.4P: NS
18 Semen parameters before preparation for insemination RESULTSSemen parameters before preparation for inseminationLetrozole31.43±4.163.9 ± 41.359.7 ± 16.152.9 ± 11.3hMG30.10±5.966.3 ± 44.462.4 ± 15.354.1 ± 9.2P valueNSAge of male partner (yrs)Concentration(x106/ml)Motility (%)Normal sperm forms (%)
20 RESULTS hMG 15 % 1(twin) 1(moderate) P value NS Letrozole 17.5% 1(triplet)Pregnancy rateMultiple pregnancyOHSS
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 ConclusionAlthough 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 ConclusionAnother 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 & phrenologyStaining uses brains preserved in formalin - and stained using an enzymeUseful for identifying functional connectionsNeuroanatomy essentially divided into 2 areas -Gross neuroanatomy - (eg Brodmann)Fine neuorantomy (eg histology)NeurophysiologyElectrical stimulation (eg Penfield)Single cell recordingsLesions (eg Experimental Ablation)
24 ConclusionDespite significantly lower E2 levels in the letrozole-treated women, endometrial development was unaffected, endometrial thickness and pattern were similar in both groups.
25 ConclusionSerious 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 letrozoleefficientcost effectivesimple and convenient