ABSTRACT
BACKGROUND: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91). CONCLUSIONS: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.
Subject(s)
Aromatase Inhibitors/therapeutic use , Nitriles/therapeutic use , Triazoles/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Aromatase Inhibitors/adverse effects , Clomiphene/adverse effects , Clomiphene/therapeutic use , Female , Fertilization in Vitro , Follicle Stimulating Hormone/adverse effects , Follicle Stimulating Hormone/therapeutic use , Gonadotropins/adverse effects , Gonadotropins/therapeutic use , Humans , Infertility, Female/prevention & control , Letrozole , Middle Aged , Neoplasms/drug therapy , Nitriles/adverse effects , Ovulation Induction , Polycystic Ovary Syndrome/chemically induced , Prospective Studies , Randomized Controlled Trials as Topic , Retrospective Studies , Triazoles/adverse effectsABSTRACT
OBJECTIVE: The main objectives of this study were to investigate whether [1] subcutaneous (SC) administration of pulsatile gonadotropin-releasing hormone (GnRH) decreases the increased levels of luteinizing hormone (LH) observed in women with polycystic ovary syndrome (PCOS); and [2] GnRH administration modifies the pattern of LH secretion observed in these patients. DESIGN: Serum follicle-stimulating hormone (FSH) and LH levels and LH pulse amplitude and pulse interval were determined in 13 patients with PCOS during the first 3 days of the cycle following the administration of 10 mg of medroxyprogesterone acetate during 5 days. SETTING: Infertility clinic. PATIENT(S): Thirteen women with PCOS. INTERVENTION(S): Determination of FSH and LH serum levels after SC administration of pulsatile GnRH. MAIN OUTCOME MEASURE(S): The FSH and LH levels in serum. RESULT(S): Mean FSH and LH levels in serum decreased following the administration of subcutaneous pulsatile GnRH in all treated women compared with baseline values. The LH pulse amplitude and pulse interval decreased in all patients following the administration of pulsatile GnRH. CONCLUSION(S): The SC administration of pulsatile GnRH in women with PCOS significantly decreases FSH and LH levels in serum. A decrease in the secretion of gonadotropins, without reaching the intense suppression observed with GnRH analogues, could be of great utility in in vitro fertilization (IVF) treatments.
