Use of letrozole in assisted reproduction: a systematic review and meta-analysis.

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.

Identification of risk factors for prevention and early diagnosis of a-symptomatic post-menopausal women.

At present, healthcare for post-menopausal a-symptomatic women offers a great opportunity to identify risk factors (RFs) for prevention of diseases which cause high mortality or disability. It is always necessary to promote a healthy lifestyle and identify RFs in order to stratify people according their risk of suffering cardiovascular disease (CVD), cancer (especially of the lung, breast and colon) and osteoporosis. Cardiovascular disease is the leading cause of death. The main independent factors are: age, smoking, high blood pressure, elevated LDL, low HDL cholesterol, and diabetes. Several global risk scores, such as the Framingham score, allow us to assess the risk of suffering a fatal or severe accident in the next 10 years. According to such scores, patients are classified as high, intermediate or low-risk and several intervention strategies may be proposed. There are several genetic and reproductive factors related to breast cancer. Global risk can be assessed by means of the Gail index, which predicts both individual lifetime and 5-year risk. This allows us to recommend breast cancer chemoprevention in high-risk patients. Age, family history, previous fragility fractures, low body mass index, smoking and the administration of oral glucocorticoids are the main osteoporosis RFs. Their assessment allows the indication of bone mineral density (BMD) testing and, according to the T-score, whether to start anti-resorptive therapy. The common problem with RFs is their variability among different populations and fact that the extrapolation of data for an individual is difficult.