STUDY QUESTION
What are the results of transplanting cryopreserved ovarian tissue?
SUMMARY ANSWER
The transplanted ovarian tissue can last up to 10 years, with no relapses following the 53 ...transplantations, and the chance of a successful pregnancy is currently around one in three for those with a pregnancy-wish.
WHAT IS KNOWN ALREADY
Cryopreservation of ovarian tissue is now gaining ground as a valid method for fertility preservation. More than 36 children worldwide have now been born following this procedure.
STUDY DESIGN, SIZE, DURATION
This is a retrospective cohort study of 41 women who had thawed ovarian tissue transplanted 53 times over a period of 10 years, including 1 patient who was lost to follow-up.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The 41 Danish women, who had in total 53 transplantations, were followed for ovarian function and fertility outcome. Safety was assessed by monitoring relapse in cancer survivors.
MAIN RESULTS, AND THE ROLE OF CHANCE
Among 32 women with a pregnancy-wish, 10 (31%) had a child/children (14 children in total); this included 1 woman with a third trimester on-going pregnancy. In addition, two legal abortions and one second trimester miscarriage occurred. A total of 24 clinical pregnancies were established in the 32 women with a pregnancy-wish. The tissue remained functional for close to 10 years in some cases and lasted only a short period in others. Three relapses occurred but were unlikely to be due to the transplanted tissue.
LIMITATIONS, REASONS FOR CAUTION
Self-report through questionnaires with only in-one hospital formalised follow-up of transplanted patients could result in unreported miscarriages. The longevity of the tissue may vary by few months compared with those reported because some patients simply could not remember the date when the tissue became non-functional.
WIDER IMPLICATIONS OF THE FINDINGS
Cryopreservation of ovarian tissue is likely to become integrated into the treatment of young women, with cancer, who run a risk of losing their fertility. The full functional lifespan of grafts is still being evaluated, because many of the transplanted women have continued to maintain ovarian activity. Some of our first cases have had tissue functioning for ∼10 years.
STUDY FUNDING/COMPETING INTEREST(S)
The Child Cancer Foundation in Denmark (2012–26) and the EU interregional project ReproHigh are thanked for having funded this study. They had no role in the study design, collection and analysis of data, data interpretation or writing of the report. The authors have no conflict of interest to disclose.
Abstract
BACKGROUND
Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) ...and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility.
OBJECTIVE AND RATIONALE
With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss.
SEARCH METHODS
Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity.
OUTCOMES
Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation.
LIMITATIONS, REASONS FOR CAUTION
The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention.
WIDER IMPLICATIONS
The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss.
STUDY FUNDING/COMPETING INTEREST(S)
The work was funded by ESHRE. None of the authors has a conflict of interest.
The preparation of cold molecules is of great importance in many contexts, such as fundamental physics investigations, high-resolution spectroscopy of complex molecules, cold chemistry and ...astrochemistry. One versatile and widely applied method to cool molecules is helium buffer-gas cooling in either a supersonic beam expansion or a cryogenic trap environment. Another more recent method applicable to trapped molecular ions relies on sympathetic translational cooling, through collisional interactions with co-trapped, laser-cooled atomic ions, into spatially ordered structures called Coulomb crystals, combined with laser-controlled internal-state preparation. Here we present experimental results on helium buffer-gas cooling of the rotational degrees of freedom of MgH(+) molecular ions, which have been trapped and sympathetically cooled in a cryogenic linear radio-frequency quadrupole trap. With helium collision rates of only about ten per second--that is, four to five orders of magnitude lower than in typical buffer-gas cooling settings--we have cooled a single molecular ion to a rotational temperature of 7.5(+0.9)(-0.7) kelvin, the lowest such temperature so far measured. In addition, by varying the shape of, or the number of atomic and molecular ions in, larger Coulomb crystals, or both, we have tuned the effective rotational temperature from about 7 kelvin to about 60 kelvin by changing the translational micromotion energy of the ions. The extremely low helium collision rate may allow for sympathetic sideband cooling of single molecular ions, and eventually make quantum-logic spectroscopy of buffer-gas-cooled molecular ions feasible. Furthermore, application of the present cooling scheme to complex molecular ions should enable single- or few-state manipulations of individual molecules of biological interest.
Tardigrades are microscopic animals found worldwide in aquatic as well as terrestrial ecosystems. They belong to the invertebrate superclade Ecdysozoa, as do the two major invertebrate model ...organisms: Caenorhabditis elegans and Drosophila melanogaster. We present a brief description of the tardigrades and highlight species that are currently used as models for physiological and molecular investigations. Tardigrades are uniquely adapted to a range of environmental extremes. Cryptobiosis, currently referred to as a reversible ametabolic state induced by e.g. desiccation, is common especially among limno‐terrestrial species. It has been shown that the entry and exit of cryptobiosis may involve synthesis of bioprotectants in the form of selective carbohydrates and proteins as well as high levels of antioxidant enzymes and other free radical scavengers. However, at present a general scheme of mechanisms explaining this phenomenon is lacking. Importantly, recent research has shown that tardigrades even in their active states may be extremely tolerant to environmental stress, handling extreme levels of ionizing radiation, large fluctuation in external salinity and avoiding freezing by supercooling to below −20 °C, presumably relying on efficient DNA repair mechanisms and osmoregulation. This review summarizes the current knowledge on adaptations found among tardigrades, and presents new data on tardigrade cell numbers and osmoregulation.
The prevalence of osteoarthritis (OA) in the temporomandibular joints (TMJs) in hand OA patients is largely unknown. Our aims were to explore (1) The frequency of TMJ-related symptoms and clinical ...findings; (2) The TMJ OA frequency defined by cone beam computed tomography (CBCT); and (3) The relationship between TMJ-related symptoms/clinical findings and CBCT-defined TMJ OA, in a hand OA cohort.
We calculated the frequencies of TMJ-related symptoms, clinical findings and diagnosis of TMJ OA by CBCT and clinical examination in 54 patients from the Oslo hand OA cohort (88% women, mean (range) age 71 (61–83) years). Participants with and without CBCT-defined TMJ OA were compared for differences in proportions (95% confidence interval (CI)) of symptoms and clinical findings. Sensitivity and specificity of the clinical TMJ OA diagnosis were calculated using CBCT as reference.
Self-reported symptoms and clinical findings were found in 24 (44%) and 50 (93%) individuals (93%), respectively, whereas 7 (13%) had sought healthcare. Individuals with CBCT-defined TMJ OA (n = 36, 67%) reported statistically significantly more pain at mouth opening (22%, 95% CI 4–40%), clicking (33%, 95% CI 14–52%) and crepitus (25%, 95% CI 4–46%). By clinical examination, only crepitus was more common in TMJ OA (33%, 95% CI 29–77%). Clinical diagnosis demonstrated low sensitivity (0.42) and high specificity (0.93).
CBCT-defined TMJ OA was common in hand OA patients, suggesting that TMJ OA may be part of generalized OA. Few had sought healthcare, despite high burden of TMJ-related symptoms/findings. Clinical examination underestimated TMJ OA frequency.
Objective
Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather ...limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardiovascular adverse events in patients exposed to etoricoxib, celecoxib, or nonselective NSAIDs or totally unexposed to NSAIDs.
Methods
We performed a national register‐based cohort study on patients with AS or SpA (n = 21,872) identified in the Swedish national patient register from 1987–2009. Treatment exposure was assessed time dependently based on the prescription drug register from 2006–2009, adjusting for sociodemographics and comorbidities derived from national population‐based registers.
Results
Exposure to etoricoxib, celecoxib, and nonselective NSAIDs was 7.6%, 3.9%, and 71.2%, respectively. No major risk differences for serious cardiovascular, gastrointestinal, or renal adverse events were seen among the 3 exposure groups. Patients unexposed to NSAIDs had more baseline comorbidities and an increased relative risk for congestive heart failure events during the study period (2.0, 95% confidence interval 95% CI 1.3–3.2). The relative risk for atherosclerotic events was nonsignificant when compared to the nonselective NSAID group (1.0, 95% CI 0.7–1.5), while the relative risk for gastrointestinal events was lower for unexposed patients (0.5, 95% CI 0.4–0.7).
Conclusion
Overall, serious adverse events related to nonselective NSAIDs, etoricoxib, and celecoxib were similar and in the range of what would be expected in a group of SpA patients. Patients unexposed to NSAIDs had considerably more baseline comorbidities and increased risk for congestive heart failure, reflecting a selection of patients being prescribed NSAIDs in clinical practice.
We examined latitudinal variation in adult and larval heat tolerance in Drosophila melanogaster from eastern Australia. Adults were assessed using static and ramping assays. Basal and hardened static ...heat knockdown time showed significant linear clines; heat tolerance increased towards the tropics, particularly for hardened flies, suggesting that tropical populations have a greater hardening response. A similar pattern was evident for ramping heat knockdown time at 0.06 °C min⁻¹ increase. There was no cline for ramping heat knockdown temperature (CTmax) at 0.1 °C min⁻¹ increase. Acute (static) heat knockdown temperature increased towards temperate latitudes, probably reflecting a greater capacity of temperate flies to withstand sudden temperature increases during summer in temperate Australia. Larval viability showed a quadratic association with latitude under heat stress. Thus, patterns of heat resistance depend on assay methods. Genetic correlations in thermotolerance across life stages and evolutionary potential for critical thermal limits should be the focus of future studies.
This article explores how experienced relational quality in blended workgroups consisting of permanent and temporary members is affected by temporary members' normative expectations for the ...relationship. We draw on Axel Honneth's four primary forms of recognition to illuminate the foundation of normative expectations. This focus on temporary members' normative expectations contrasts with existing research in blended workgroups, focusing predominantly on the behavior of permanent members towards temporary ones. We draw on illustrative examples from a qualitative study of first - and third-year nursing students' experiences during their internships at somatic hospitals. First - and third-year students report how they experience a deviation from their normative expectations as a threat to their positive self-image. In conclusion, we propose that the normative expectations characterizing the relationship between nursing students and permanent nurses can be described based on three forms of recognition:' visibility,' 'respect,' and 'esteem.'
Bleeding has recently emerged as an important outcome in the management of acute coronary syndromes (ACS), which is relatively frequent compared with ischaemic outcomes and has important implications ...in terms of prognosis, outcomes, and costs. In particular, there is evidence that patients experiencing major bleeding in the acute phase are at higher risk for death in the following months, although the causal nature of this relation is still debated. This position paper aims to summarize current knowledge regarding the epidemiology of bleeding in ACS and percutaneous coronary intervention, including measurement and definitions of bleeding, with emphasis on the recent consensus Bleeding Academic Research Consortium (BARC) definitions. It also provides an European perspective on management strategies to minimize the rate, extent, and consequences of bleeding. Finally, the research implications of bleeding (measuring and reporting bleeding in trials, the importance of bleeding as an outcome measure, and bleeding as a subject for future research) are also discussed.
Variability in the effect of subcutaneously administered insulin represents a major challenge in insulin therapy where precise dosing is required in order to achieve targeted glucose levels. Since ...this variability is largely influenced by the absorption of insulin, a deeper understanding of the factors affecting the absorption of insulin from the subcutaneous tissue is necessary in order to improve glycaemic control and the long-term prognosis in people with diabetes. These factors can be related to either the insulin preparation, the injection site/patient, or the injection technique. This review highlights the factors affecting insulin absorption with special attention on the physiological factors at the injection site. In addition, it also provides a detailed description of the insulin absorption process and the various modifications to this process that have been utilized by the different insulin preparations available.
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