Research question: How does follicle distribution evolve in the human ovarian cortex between the ages of 20 and 35? Design: Fragments of ovarian cortex from women who underwent unilateral oophorectomy for fertility preservation were obtained for quantitative histological assessment, including recording of the two-dimensional coordinates of follicles. Data were analysed using spatial statistical methods. Results:From 14 patients aged 20-35 years, 53 ovarian cortex tissue samples were obtained, containing 1-803 follicles. Primordial and transitory follicles lay in a clustered manner in the human ovarian cortex, with an average cluster radius of ~ 270 μm (95% CI range 154 -377 µm; n = 49). Follicle density declined with age (p = 0.006, n = 13) and the distance to the nearest neighbouring follicle increased (p = 0.004, n = 13). The cluster radius decreased with age (p = 0.02, n = 13), but the degree of clustering tended to increase (p = 0.11, n = 13). In the majority of the samples, follicles of different stages lay in different clusters (p < 0.05, n = 13). Conclusions:This study shows that primordial and transitory follicles lie in different clusters in the human ovarian cortex. Spatiotemporal computer simulation suggests that interfollicular signals may hinder follicle loss and therefore may drive clustered follicle distribution. In clinical practice, the patient's age should be taken into account when assessing follicle density, as follicle distribution is increasingly clustered with advancing age.
Objective This study explores how treatment with intratympanic steroid injection affects quality of life, as well as several subjective complaints in patients with Ménière's disease. Methods Patients filled in the Ménière's Disease Outcome Questionnaire (MDOQ) and answered questions about subjective complaints. Scores before and after treatment were compared using paired t tests. Results Forty‐nine patients treated with intratympanic steroid injection were included. Quality of life was improved in 36 (73%) patients, the same in 9 (18%) patients, and lower in 4 (8%) patients. Overall, the mean change in MDOQ was +20.6 points (95% confidence interval +14.5 to +26.7 points, p < 0.001). The improvement was seen in the emotional, physical, and mental domain. Most patients experienced less vertigo and instability but did not notice change in subjective hearing, tinnitus, or aural fullness after treatment. Conclusion Treatment with intratympanic steroid injection leads to an improvement in quality of life in most patients. Moreover, the procedure is only minimally invasive. Based on the findings in this study, treatment with ITS should be discussed with every patient suffering from vertigo attacks due to active Ménière's disease. Level of evidence Level 4
IntroductionOutcomes of surgery for Ménière’s disease (MD) remain discordant. Recently, a new surgical procedure in which the endolymphatic duct is clipped was proposed. To date, only one prospective trial assessing this technique was published, yielding promising results. This protocol describes a prospective, double-blinded, randomised controlled trial that will be carried out to assess the effectiveness of this surgical intervention.MethodsEighty-four patients with intractable MD will be recruited from 13 hospitals in the Netherlands. Intraoperatively, randomisation will determine whether endolymphatic duct blockage (EDB) or endolymphatic sac decompression (ESD) will be performed. Randomisation will be 1:1 stratified for gender and duration of MD (recent-onset versus mature MD). All participants receive vestibular rehabilitation after surgery. Patients are followed up during 1 year after surgery. Follow-up visits will take place at 1 week, 3 months, 6 months and 12 months after surgery. The main study endpoint is proportion of patients who are free of vertigo spells at 12 months postoperatively. Secondary parameters include cumulative number of vertigo bouts, co-intervention, tinnitus, hearing, quality of life, cost effectiveness and a budget impact analysis. Total duration of the study is 4 years.AnalysisThe primary analysis will follow the intention-to-treat principle. For the primary outcome, a χ2 test will be performed. Secondary outcomes will be analysed using a linear mixed model (EDB versus decompression group) at the different time measurement point.Ethics and disseminationThis study was reviewed and approved by a board of specialists before funding was obtained, as well as by the Medical Research Ethics Committee Leiden-The Hague-Delft and the boards of all participating centres. Results of this study will be published in international peer-reviewed scientific journals and will be presented on (inter)national scientific conferences and meetings.Trial registration numbersNL9095 and ISRCTN12074571; Pre-Results.
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