FSH prevents depletion of the resting follicle pool by promoting follicular number and morphology in fresh and cryopreserved primate ovarian tissues following xenografting

Background: Cryopreservation and transplantation of ovarian tissue is one option for re-establishing ovarian function, but optimal conditions for graft sustainment and follicular survival are still considered experimental. The present study aims to analyze the effect of FSH treatment on the resting follicle pool in fresh and cryopreserved primate ovarian tissues following xenografting. Methods: Ovarian tissues from adult marmosets were grafted freshly or following cryopreservation to ovarectomized nude mice treated with FSH 25 IU twice daily post transplantation or left untreated as controls. Grafts were retrieved 2 or 4 weeks after transplantation to evaluate the number and morphological appearance of follicles. Results: Early start of FSH treatment within 1 week following transplantation partly prevents primordial follicle loss in fresh and frozen-thawed tissues, whereas after a 3 weeks time interval this effect is present only in fresh tissues. A similar positive effect of early, but not later FSH treatment on primary follicles is seen in fresh tissues compared to only marginal effects in frozen-thawed tissues. The percentage of morphologically normal follicles is generally increased in FSH treated tissues, whereas the percentage of primary follicles over all primordial and primary follicles is increased by FSH only in freshly-grafted tissues. Conclusions: FSH treatment alleviates depletion of the resting follicle pool and promotes normal follicular morphology both in freshly and frozen-thawed grafted tissues. In previously cryopreserved tissues, applying to most of the tissues intended for clinical use in fertility preservation attempts, its positive effect on primordial follicle numbers and potential graft sustainment is dependent on an early start of treatment within one week of transplantation

Dynamics of notch pathway expression during mouse testis post-natal development and along the spermatogenic cycle

Articles in International JournalsThe transcription and expression patterns of Notch pathway components (Notch 1–3, Delta1 and 4, Jagged1) and effectors (Hes1, Hes2, Hes5 and Nrarp) were evaluated (through RT-PCR and IHC) in the mouse testis at key moments of post-natal development, and along the adult spermatogenic cycle. Notch pathway components and effectors are transcribed in the testis and expressed in germ, Sertoli and Leydig cells, and each Notch component shows a specific cell-type and timewindow expression pattern. This expression at key testis developmental events prompt for a role of Notch signaling in prepubertal spermatogonia quiescence, onset of spermatogenesis, and regulation of the spermatogenic cycle

Elevated follicle-stimulating hormone levels and the chances for azoospermic men to become fathers after retrieval of elongated spermatids from cryopreserved testicular tissue

OBJECTIVE: To assess individual chances for a live-born child in azoospermic men by performance of testicular sperm extraction (TESE) followed by intracytoplasmatic sperm injection (ICSI). DESIGN: A retrospective cohort study. SETTING: An academic fertility care center and research unit. PATIENT(S): Two hundred three couples who wished to have a child; all men had azoospermia. INTERVENTION(S): All men were operated for TESE; 112 men were found to have elongated spermatids (ES), and 209 ICSI cycles were performed in these men using cryopreserved tissue. MAIN OUTCOME MEASURE(S): Predictors for the chances to obtain live sperm and for probabilities of fertilization, clinical pregnancies, and live births. RESULT(S): Testicular volume, FSH, and inhibin B levels were predictors for the presence of ES. Intracytoplasmic sperm injection resulted in 23 pregnancies, leading to 20 live births. Despite the presence of ES and performance of ICSI in cases of FSH levels >or=20 IU/L, no pregnancy resulted in these men (n = 21). Receiver operating characteristics revealed FSH levels of >or=20 IU/L as cutoff for treatment success. The number of testicular tubuli containing ES served as a predictor for clinical pregnancy as well as for live birth. Cigarette smoking by the male partner exerted a significant negative influence on treatment success. CONCLUSION(S): The degree of completely maintained spermatogenesis within the biopsy appears to reflect intrinsic abilities of spermatozoa to induce normal embryo development. Charts based on regression models are presented for counseling patients before TESE; these explain chances of finding ES and probability of successful ICSI. Obtaining offspring is unlikely in cases of azoospermia and of FSH levels of >or=20 IU/L

Efficacy and safety of pharmacotherapy for Alzheimer’s disease and for behavioural and psychological symptoms of dementia in older patients with moderate and severe functional impairments: a systematic review of controlled trials

Background: Many patients with Alzheimer's disease (AD) are physically frail or have substantial functional impairments. There is growing evidence that such patients are at higher risk for medication-induced adverse events. Furthermore, frailty seems to be more predictive of poor clinical outcomes than chronological age alone. To our knowledge, no systematic review of clinical trials examining drug therapy of AD or behavioural and psychological symptoms of dementia (BPSD) has specifically focused on the topic of physical frailty. Our objective was to evaluate the efficacy and safety of pharmacotherapy in AD patients with frailty or significant functional impairments. Methods: We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) of drug therapy of AD and BPSD in patients with significant functional impairments according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Cochrane research criteria. Significant functionally impaired patient populations were identified using the recommendations of the Medication and Quality of Life in frail older persons (MedQoL) Research Group. Screening, selection of studies, data extraction and risk of bias assessment were performed independently by two reviewers. Outcomes including functional status, cognitive function, changes in BPSD symptoms, clinical global impression and quality of life were analysed. For assessing harm, we assessed adverse events, drop-outs as a proxy for treatment tolerability and death. Results were analysed according to Cochrane standards and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Of 45,045 search results, 38,447 abstracts and 187 full texts were screened, and finally, 10 RCTs were included in the systematic review. Selected articles evaluated pharmacotherapy with acetylcholinesterase-inhibitors (AChEI), anticonvulsants, antidepressants and antipsychotics. Studies of AChEIs suggested that patients with significant functional impairments had slight but significant improvements in cognition and that AChEIs were generally well tolerated. Studies of antidepressants did not show significant improvements in depressive symptoms. Antipsychotics and anticonvulsants showed small effects on some BPSD items but also higher rates of adverse events. However, due to the very small number of identified trials, the quality of evidence for all outcomes was low to very low. Overall, the small number of eligible studies demonstrates that significantly functional impaired older patients have not been adequately taken into consideration in most clinical trials investigating drug therapy of AD and BPSD. Conclusion: Due to lack of evidence, it is not possible to give specific recommendations for drug therapy of AD and BSPD in frail older patients or older patients with significant functional impairments. Therefore, clinical trials focussing on frail older adults are urgently required. A standardized approach to physical frailty in future clinical studies is highly desirable