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

Increasing intraovarian Increases endogenous production of FSH Enhances ovarian response to gonadotropin stimulation Suppressing estrogen 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 a) Unexplained infertility b) PCO c) Poor responders Ovulation induction

IUI Human reproduction Mitwally et al. 2003 Clinical pregnancy rate 25 20 15 Clinical pregnancy rate 19.1% 10 18.7% 10.5% 5 FSH-only Letrozole- FSH CC-FSH

IUI Fertility and Sterility Healey et al. 2003 Clinical pregnancy rate 25 20 15 Clinical pregnancy rate 21.6% 20.9% 10 5 FSH FSH+Letrozole

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

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)

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

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

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

Letrozole vs hMG Letrozole 2x1 hMG hMG 1x75ıu (<30 years) Day 3 Day 7 Day 3 Day 7 HCG Letrozole 2x1 hMG 1x75ıu (<30 years) hMG hMG 1x150ıu(30years)

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

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

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 (%)

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

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

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.

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. 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)

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

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