BackgroundFor the last year we have been treating normal responders with gonadotropins and letrozole during the whole stimulation in order to improve response to FSH by increasing the intrafollicular androgen concentration, and to reduce circulating estrogen concentrations. The aim of this study was to compare the IVF outcome of normal responders treated with letrozole and gonadotropins during ovarian stimulation with patients treated with gonadotropins only.MethodsA single centre retrospective cohort study of 174 patients (87 in each group).ResultsThe age of the patients was comparable between the groups. Estradiol levels were significantly higher in the control group (6760 pmol/L vs. 2420 pmol/L respectively, p < 0.01), and the number of follicles ≥15 mm at the trigger day was significantly lower in the control group (7.9 vs. 10, p = 0.02). The number of retrieved oocytes (10 vs. 14.5, p < 0.01), MII oocytes (7.9 vs. 11.2, p < 0.01) and blastocysts (2.7 vs. 4.0, p = 0.02) was significantly higher in the study group. We found no significant differences in the cumulative pregnancy outcome between the two groups (65.2% vs 58.3% p = NS).ConclusionsWe conclude that co-treatment with letrozole improves the IVF outcome in normal responders in terms of increased number of blastocysts obtained without increasing the pregnancy rate or the risk of OHSS.

Background Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques. Methods Women undergoing standard wire or magnetic seed localization for non-palpable lesions between August 2018 and August 2020 were recruited prospectively to this IDEAL stage 2a/2b platform cohort study. The primary outcome was effectiveness defined as accurate localization and removal of the index lesion. Secondary endpoints included safety, specimen weight and reoperation rate for positive margins. Results Data were accrued from 2300 patients in 35 units; 2116 having unifocal, unilateral breast lesion localization. Identification of the index lesion in magnetic-seed-guided (946 patients) and wire-guided excisions (1170 patients) was 99.8 versus 99.1 per cent (P = 0.048). There was no difference in overall complication rate. For a subset of patients having a single lumpectomy only for lesions less than 50 mm (1746 patients), there was no difference in median closest margin (2 mm versus 2 mm, P = 0.342), re-excision rate (12 versus 13 per cent, P = 0.574) and specimen weight in relation to lesion size (0.15 g/mm2  versus 0.138 g/mm2, P = 0.453). Conclusion Magnetic seed localization demonstrated similar safety and effectiveness to those of wire localization. This study has established a robust platform for the comparative evaluation of new localization devices.

BackgroundPrevious studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only.MethodsA single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits.ResultsThe age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups.The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17.3 ng/ml p < 0.001) were significantly decreased in the letrozole group.ConclusionsOpposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.