A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys

STUDY QUESTION What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males? SUMMARY ANSWER Based on a review of the clinical literature and research evidence for sperm freezing and testicular tissue cryopreservation, and after consideration of the relevant ethical and legal challenges, an algorithm for the cryopreservation of sperm and testicular tissue is proposed for prepubertal boys and adolescent males at high risk of fertility loss. WHAT IS KNOWN ALREADY A known late effect of the chemotherapy agents and radiation exposure regimes used to treat childhood cancers and other non-malignant conditions in males is the damage and/or loss of the proliferating spermatogonial stem cells in the testis. Cryopreservation of spermatozoa is the first line treatment for fertility preservation in adolescent males. Where sperm retrieval is impossible, such as in prepubertal boys, or it is unfeasible in adolescents prior to the onset of ablative therapies, alternative experimental treatments such as testicular tissue cryopreservation and the harvesting and banking of isolated spermatogonial stem cells can now be proposed as viable means of preserving fertility. STUDY DESIGN, SIZE, DURATION Advances in clinical treatments, patient management strategies and the research methods used to preserve sperm and testicular tissue for prepubertal boys and adolescents were reviewed. A snapshot of the up-take of testis cryopreservation as a means to preserve the fertility of young males prior to December 2012 was provided using a questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS A comprehensive literature review was conducted. In addition, survey results of testis freezing practices in young patients were collated from 24 European centres and Israeli University Hospitals. MAIN RESULTS AND THE ROLE OF CHANCE There is increasing evidence of the use of testicular tissue cryopreservation as a means to preserve the fertility of pre- and peri-pubertal boys of up to 16 year-old. The survey results indicate that of the 14 respondents, half of the centres were actively offering testis tissue cryobanking as a means of safeguarding the future fertility of boys and adolescents as more than 260 young patients (age range less than 1 year old to 16 years of age), had already undergone testicular tissue retrieval and storage for fertility preservation. The remaining centres were considering the implementation of a tissue-based fertility preservation programme for boys undergoing oncological treatments. LIMITATIONS, REASONS FOR CAUTION The data collected were limited by the scope of the questionnaire, the geographical range of the survey area, and the small number of respondents. WIDER IMPLICATIONS OF THE FINDINGS The clinical and research questions identified and the ethical and legal issues raised are highly relevant to the multi-disciplinary teams developing treatment strategies to preserve the fertility of prepubertal and adolescent boys who have a high risk of fertility loss due to ablative interventions, trauma or genetic pre-disposition. STUDY FUNDING/COMPETING INTEREST(S) The work was funded by the European Society of Human Reproduction and Embryology (ESHRE)

Association of alcohol screening scores with adverse mental health conditions and substance use among US adults.

Importance: Alcohol screening may be associated with health outcomes that cluster with alcohol use (ie, alcohol-clustering conditions), including depression, anxiety, and use of tobacco, marijuana, and illicit drugs. Objective: To quantify the extent to which alcohol screening provides additional information regarding alcohol-clustering conditions and to compare 2 alcohol use screening tools commonly used for this purpose. Design, Setting, and Participants: This longitudinal cohort study used data from the Veterans Aging Cohort Study. Data were collected at 8 Veterans Health Administration facilities from 2003 through 2012. A total of 7510 participants were enrolled, completed a baseline survey, and were followed up. Veterans with HIV were matched with controls without HIV by age, race, sex, and site of care. Data were analyzed from January 2019 to December 2019. Exposures: The Alcohol Use Disorders Identification Test (AUDIT) and Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) were used to assess alcohol use, with 4 risk groups delineated for each test: score 0 to 7 (reference), score 8 to 15, score 16 to 19, and score 20 to 40 (maximum score) for the full AUDIT and score 0 to 3 (reference), score 4 to 5, score 6 to 7, and score 8 to 12 (maximum score) for the AUDIT-C. Main Outcomes and Measures: Alcohol-clustering conditions, including self-reported symptoms of depression and anxiety and use of tobacco, marijuana, cocaine, other stimulants, opioids, and injection drugs. Results: A total of 6431 US patients (6104 [95%] men; median age during survey years 2003-2004, 50 years [range, 28-86 years; interquartile range, 44-55 years]) receiving care in the Veterans Health Administration completed 1 or more follow-up surveys when the AUDIT was administered and were included in the present analyses. Of the male participants, 4271 (66%) were African American, 1498 (24%) were white, and 590 (9%) were Hispanic. The AUDIT and AUDIT-C scores were associated with each alcohol-clustering condition. In particular, an AUDIT score of 20 or higher (vs <8, the reference) was associated with symptoms of depression (odds ratio [OR], 8.37; 95% CI, 6.20-11.29) and anxiety (OR, 8.98; 95% CI, 6.39-12.60) and with self-reported use of tobacco (OR, 14.64; 95% CI, 8.94-23.98), marijuana (OR, 12.41; 95% CI, 8.61-17.90), crack or cocaine (OR, 39.47; 95% CI, 27.38-56.90), other stimulants (OR, 21.31; 95% CI, 12.73-35.67), and injection drugs (OR, 8.67; 95% CI, 5.32-14.13). An AUDIT score of 20 or higher yielded likelihood ratio (sensitivity / 1 - specificity) values greater than 3.5 for depression, anxiety, crack or cocaine use, and other stimulant use. Associations between AUDIT-C scores and alcohol-clustering conditions were more modest. Conclusions and Relevance: Alcohol screening can inform decisions about further screening and diagnostic assessment for alcohol-clustering conditions, particularly for depression, anxiety, crack or cocaine use, and other stimulant use. Future studies using clinical diagnoses rather than screening tools to assess alcohol-clustering conditions may be warranted