The risk of hypogonadism after testicular sperm extraction in men with various types of azoospermia: a prospective cohort study.

RESEARCH QUESTION: What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)? DESIGN: This prospective longitudinal cohort study was carried out between 2007 and 2015. RESULTS: Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT. CONCLUSIONS: Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE.

Successful restoration of spermatogenesis following gender-affirming hormone therapy in transgender women.

Increasing numbers of transgender individuals are presenting for gender-affirming medical care. For trans women, gender-affirming hormone therapy (GAHT) promotes feminization but also inhibits spermatogenesis. There is a common untested assumption that this inhibition is permanent, resulting in infertility. In this longitudinal study, we report the recovery of viable spermatozoa in nine trans women who stopped GAHT for reproductive purposes. Our preliminary findings suggest that the negative impact of GAHT on spermatogenesis can be reversed, casting doubt on previous claims that GAHT in trans women inevitably leads to permanent infertility. Larger studies are needed to confirm our findings, which have implications not only for fertility counseling and the reproductive options of transgender individuals but also efforts to restrict access to GAHT based on fertility grounds.

Childhood cancer and hematological disorders negatively affect spermatogonial quantity at diagnosis: a retrospective study of a male fertility preservation cohort.

STUDY QUESTION: What is the impact of cancer or hematological disorders on germ cells in pediatric male patients? SUMMARY ANSWER: Spermatogonial quantity is reduced in testes of prepubertal boys diagnosed with cancer or severe hematological disorder compared to healthy controls and this reduction is disease and age dependent: patients with central nervous system cancer (CNS tumors) and hematological disorders, as well as boys <7 years are the most affected. WHAT IS KNOWN ALREADY: Fertility preservation in pediatric male patients is considered based on the gonadotoxicity of selected treatments. Although treatment effects on germ cells have been extensively investigated, limited data are available on the effect of the disease on the prepubertal male gonad. Of the few studies investigating the effects of cancer or hematologic disorders on testicular function and germ cell quantity in prepuberty, the results are inconsistent. However, recent studies suggested impairments before the initiation of known gonadotoxic therapy. Understanding which diseases and at what age affect the germ cell pool in pediatric patients before treatment is critical to optimize strategies and counseling for fertility preservation. STUDY DESIGN, SIZE, DURATION: This multicenter retrospective cohort study included 101 boys aged <14 years with extra-cerebral cancer (solid tumors), CNS tumors, leukemia/lymphoma (blood cancer), or non-malignant hematological disorders, who were admitted for a fertility preservation programme between 2002 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: In addition to clinical data, we analyzed measurements of testicular volume and performed histological staining on testicular biopsies obtained before treatment, at cryopreservation, to evaluate number of spermatogonia per tubular cross-section, tubular fertility index, and the most advanced germ cell type prior to chemo-/radiotherapy. The controls were data simulations with summary statistics from original studies reporting healthy prepubertal boys' testes characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Prepubertal patients with childhood cancer or hematological disorders were more likely to have significantly reduced spermatogonial quantity compared to healthy controls (48.5% versus 31.0% prevalence, respectively). The prevalence of patients with reduced spermatogonial quantity was highest in the CNS tumor (56.7%) and the hematological disorder (55.6%) groups, including patients with hydroxyurea pre-treated sickle cell disease (58.3%) and patients not exposed to hydroxyurea (50%). Disease also adversely impacted spermatogonial distribution and differentiation. Irrespective of disease, we observed the highest spermatogonial quantity reduction in patients <7 years of age. LIMITATIONS, REASONS FOR CAUTION: For ethical reasons, we could not collect spermatogonial quantity data in healthy prepubertal boys as controls and thus deployed statistical simulation on data from literature. Also, our results should be interpreted considering low patient numbers per (sub)group. WIDER IMPLICATIONS OF THE FINDINGS: Cancers, especially CNS tumors, and severe hematological disorders can affect spermatogonial quantity in prepubertal boys before treatment. Consequently, these patients may have a higher risk of depleted spermatogonia following therapies, resulting in persistent infertility. Therefore, patient counseling prior to disease treatment and timing of fertility preservation should not only be based on treatment regimes, but also on diagnoses and age. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Marie Curie Initial Training Network (ITN) (EU-FP7-PEOPLE-2013-ITN) funded by European Commision grant no. 603568; ZonMW Translational Adult stem cell research (TAS) grant no. 116003002. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

The meV XUV-RIXS facility at UE112-PGM1 of BESSY II.

Resonant inelastic X-ray scattering in the XUV-regime has been implemented at BESSY II, pushing for a few-meV bandwidth in inelastic X-ray scattering at transition metal M-edges, rare earth N-edges and the K-edges of light elements up to carbon with full polarization control. The new dedicated low-energy beamline UE112-PGM1 has been designed to provide 1 µm vertical and 20 µm horizontal beam dimensions that serve together with sub-micrometre solid-state sample positioning as the source point for a high-resolution plane grating spectrometer and a high-transmission Rowland spectrometer for rapid overview spectra. The design and commissioning results of the beamline and high-resolution spectrometer are presented. Helium autoionization spectra demonstrate a resolving power of the beamline better than 10 000 at 64 eV with a 300 lines mm-1 grating while the measured resolving power of the spectrometer in the relevant energy range is 3000 to 6000.

Spermatogonial Stem Cell-Based Therapies: Taking Preclinical Research to the Next Level.

Fertility preservation via biobanking of testicular tissue retrieved from testicular biopsies is now generally recommended for boys who need to undergo gonadotoxic treatment prior to the onset of puberty, as a source of spermatogonial stem cells (SSCs). SSCs have the potential of forming spermatids and may be used for therapeutic fertility approaches later in life. Although in the past 30 years many milestones have been reached to work towards SSC-based fertility restoration therapies, including transplantation of SSCs, grafting of testicular tissue and various in vitro and ex vivo spermatogenesis approaches, unfortunately, all these fertility therapies are still in a preclinical phase and not yet available for patients who have become infertile because of their treatment during childhood. Therefore, it is now time to take the preclinical research towards SSC-based therapy to the next level to resolve major issues that impede clinical implementation. This review gives an outline of the state of the art of the effectiveness and safety of fertility preservation and SSC-based therapies and addresses the hurdles that need to be taken for optimal progression towards actual clinical implementation of safe and effective SSC-based fertility treatments in the near future.

A cohort study on factors impairing semen quality in transgender women.

BACKGROUND: Transgender women (people assigned male genders at birth with female gender identities) can choose to cryopreserve semen before their medical transition, to retain the possibility to parent genetically related offspring later in life. Our previous retrospective study showed that semen quality in transgender women was decreased compared with the general population. The etiology of this impaired semen quality remains largely unknown. However, impaired semen quality might be related to habitual behavior more typically observed in transgender women, for example, the desire to hide their testicles because of genital dysphoria. Therefore, we decided to conduct a consecutive study with prospectively obtained data on behavior and lifestyle in transgender women. OBJECTIVE: This study aimed to study the influence of a low ejaculation frequency, wearing tight undergarments, and bringing the testes in the inguinal position (tucking) on semen quality in transgender women at the time of fertility preservation. STUDY DESIGN: In this cohort study, transgender women were included between May 2018 and September 2020, at the time of fertility counseling, before the start of hormonal treatment. Data were collected on demographics, lifestyle factors, medical history, endocrine laboratory results, and semen parameters. Semen parameters were categorized using reference values for human semen of the World Health Organization and compared with semen quality in the general population. The odds ratios with 95% confidence intervals were calculated using multivariable logistic regression analysis to assess the impact of tucking, wearing tight undergarments, and a low ejaculation frequency on semen quality, correcting for potential confounders. RESULTS: Overall, 113 transgender women were included. Median semen parameters were significantly decreased than the general population. Crude logistic regression analyses showed an association between always wearing tight undergarments (odds ratio, 3.06; 95% confidence interval, 1.11-8.49) and extensive tucking (odds ratio, 6.09; 95% confidence interval, 1.54-24.01) on having a total motile sperm count of <5 million. Multivariable analyses showed that the association with tucking was independent of demographic factors, lifestyle factors, and medical history (odds ratio, 7.95; 95% confidence interval, 1.66-37.99). However, this was not the case for the association with always wearing tight undergarments (odds ratio, 2.89; 95% confidence interval, 0.95-8.82). Ejaculation frequency did not influence total motile sperm count. CONCLUSION: Behavioral factors, including wearing tight undergarments and extensive tucking, may contribute to the lower semen quality in transgender women. These results will enable optimization of fertility counseling on how to adjust lifestyle before pursuing semen cryopreservation.

Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Male patients with childhood, adolescent, and young adult cancer are at an increased risk for infertility if their treatment adversely affects reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of interventions that preserve fertility. As part of the PanCareLIFE Consortium, in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in male patients who are diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. Recognising the need for global consensus, this clinical practice guideline used existing evidence and international expertise to rigorously develop transparent recommendations that are easy to use to facilitate the care of male patients with childhood, adolescent, and young adult cancer who are at high risk of fertility impairment and to enhance their quality of life.

[Evaluation of the project for the introduction of bystander resuscitation in schools in North Rhine-Westphalia]. / Evaluation des Projekts zur Einführung von Laienreanimation an Schulen in Nordrhein-Westfalen.

BACKGROUND: Teaching of resuscitation measures is not mandatory in all schools in Germany. It is currently limited to individual, partly mandatory projects despite a low bystander resuscitation rate. For this reason, the Ministry for Schools and Education of North Rhine-Westphalia initiated the project "Bystander resuscitation at schools in NRW" in March 2017. OBJECTIVE: The aim of this work was to evaluate this project. MATERIAL AND METHODS: All secondary schools in North Rhine-Westphalia were invited to participate in the project. Medical partners from each administrative district took part, who carried out resuscitation training with existing concepts for teacher or student training. After a 3-year period, the evaluation was carried out using standardized questionnaires for school headmasters, teachers and students. RESULTS: In total, more than 40,000 pupils from 249 schools in NRW could be trained in resuscitation within the project with 6 different concepts. Of the students 85% answered the questions regarding resuscitation correctly and overall felt safe in resuscitation measures. The one-off investment requirement for all schools is roughly 4-6.5 million € and around 340,000 € in each budget year. CONCLUSION: A legal constitution and funding are necessary for a nationwide introduction of resuscitation in schools. All established concepts are effective, therefore each school can use them exactly according to their needs, optimally in a stepped form. Training for teachers should focus on resuscitation.

The relative importance of genetic parenthood.

RESEARCH QUESTION: How much do patients with severe infertility and their gynaecologists value genetic parenthood relative to other key treatment characteristics? DESIGN: A discrete choice experiment included the following treatment characteristics: genetic parenthood, pregnancy rate, curing infertility, maternal health, child health and costs. The questionnaire was disseminated between 2015 and 2016 among Dutch and Belgian patients with severe infertility and their gynaecologists. RESULTS: The questionnaire was completed by 173 patients and 111 gynaecologists. When choosing between treatments that varied in safety, effectiveness and costs, the treatment's ability to lead to genetic parenthood did not affect the treatment preference of patients with severe infertility (n = 173). Genetic parenthood affected the treatment preference of gynaecologists (n = 111) less than all other treatment characteristics. Patients indicated that they would switch to a treatment that did not enable genetic parenthood in return for a child health risk reduction of 3.6%, a cost reduction of €3500, an ovarian hyperstimulation risk reduction of 4.6%, a maternal cancer risk reduction of 2.7% or a pregnancy rate increase of 18%. Gynaecologists made similar trade-offs. CONCLUSIONS: While awaiting replication of this study in larger populations, these findings challenge the presumed dominant importance of genetic parenthood. This raises questions about whether donor gametes could be presented as a worthy alternative earlier in treatment trajectories and whether investments in novel treatments enabling genetic parenthood, like in-vitro gametogenesis, are proportional to their future clinical effect.

Use of Fertility Preservation Among a Cohort of Transgirls in the Netherlands.

PURPOSE: The primary aims of the study are to examine the rate of attempted fertility preservation (FP) among a Dutch cohort of transgirls who started gonadotropin-releasing hormone analog treatment and the reasons why adolescents did or did not choose to attempt FP. METHODS: The study was a single-center retrospective review of medical records of 35 transgirls who started gonadotropin-releasing hormone analog treatment between 2011 and 2017. RESULTS: Ninety-one percent of adolescents were counseled on the option of FP. Thirty-eight percent of counseled adolescents attempted FP, and 75% of them were able to cryopreserve sperm suitable for intrauterine insemination or intracytoplasmic sperm injection. Younger and Caucasian transgirls were less likely to attempt FP. No specific reason for declining FP was known in 33% adolescents, 32% of adolescents were not able to produce a semen sample because of early puberty, 17% felt uncomfortable with masturbation, 17% did not want to have children, and 13% wanted to adopt. CONCLUSIONS: One third of adolescents attempted FP, which is much more than the percentage reported in previous studies from the United States. One third of the transgirls could not make use of FP because they were unable to produce a semen sample because of early pubertal stage. For these adolescents, alternatives need to be explored.

Orchidopexy for bilateral undescended testes: A multicentre study on its effects on fertility and comparison of two fixation techniques.

To evaluate fertility potential after orchidopexy for bilateral undescended testis and compare two surgical fixation techniques for effect on fertility. Men older than 22 years who had either tunica albuginea orchidopexy (TAO) or "no-touch" technique (NTO) in childhood for bilateral undescended testis (BUDT) were selected. Participants filled out a questionnaire followed by physical examination, had testicular ultrasound, blood sample and semen analysis. Statistical testing was performed using general linear modelling. Sixty-seven out of 166 individuals responded. Forty-nine completed the questionnaire, and nine (18.3%) reported having fathered children. Thirty-six showed up for further examination, 26 had TAO and 10 NTO. Impaired hormonal spermatogenesis regulation (34.6% vs. 20%), higher subfertility rate (46% vs. 20%) and lower means of motile spermatozoa (58.1 × 106 spz vs. 177.9 × 106 spz) were observed in the TAO versus the NTO group; none of these were statistically significant. Four (15.4%) of the TAO and two (20%) of the NTO group have azoospermia. Although the operation technique did not have a significant impact on fertility, unfavourable outcomes were more common after surgery involving the tunica albuginea of the testis. Larger sample sizes are needed to ascertain whether the trends favouring the NTO technique are of any significance.

The risk of TESE-induced hypogonadism: a systematic review and meta-analysis.

BACKGROUND: Testicular sperm extraction (TESE) is a surgical procedure to retrieve spermatozoa from the testes of men with azoospermia to help them achieve biological parenthood. Although effective, the surgical procedure is not without complications and haematoma, devascularization, inflammation and a decrease in testosterone levels have been described as such. The prevalence and duration of hypogonadism and associated symptoms after TESE have not been studied systematically. OBJECTIVE AND RATIONALE: In this systematic review we addressed the following research questions: Are serum testosterone levels decreased after TESE and, if so, do these levels recover over time? What is the prevalence of symptoms and signs related to hypogonadism after TESE and are they related to testosterone levels? SEARCH METHODS: We searched the databases Pubmed and Embase from 1 January 1993 to 26 June 2017. We combined subject headings with terms in title and/or abstract for participants, intervention and outcomes. We included all studies that reported on TESE, regardless of the specific technique used, that measured testosterone and/or LH, and/or had information on signs or symptoms related to hypogonadism as defined by hypogonadism guidelines. An additional inclusion criterion was that studies described these measurements both before and after TESE. The quality of the included studies was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions tool. OUTCOMES: We identified 15 studies reporting on total testosterone levels of which five studies also reported on testicular volume and one study on erectile dysfunction. Men with Klinefelter syndrome and men with non-obstructive azoospermia had the strongest decrease in total testosterone levels 6 months after TESE, with a mean decrease of 4.1 and 2.7 nmol/l, respectively, which recovered again to baseline levels 26 and 18 months after TESE, respectively. At 6 months after TESE, some studies reported serum total testosterone concentrations below a cut-off value of 12 nmol/l, where symptoms and signs related to hypogonadism may appear. Furthermore, an increased prevalence of erectile dysfunction related to decreased total testosterone levels 6 months after TESE was reported. Also, in some men a decrease in testicular volume was reported. However, it is not clear if this is related to low testosterone levels. WIDER IMPLICATIONS: The transient, but statistically significant, decrease in total testosterone levels indicates that men are at risk of developing a temporary hypogonadism after TESE, but there is insufficient evidence for whether patients actually experience clinical symptoms in case of decreased serum testosterone levels. To be able to properly counsel TESE patients, more large-scale monitoring on signs and symptoms of hypogonadism, in combination with testosterone measurements, needs to be performed in men undergoing TESE.

Behavioral, cognitive, and motor performance and physical development of five-year-old children who were born after intracytoplasmic sperm injection with the use of testicular sperm.

OBJECTIVE: To evaluate at the age of 5 years the behavioral, cognitive, and motor performance and physical development of children born after testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). DESIGN: A prospective longitudinal cohort study. SETTING: Two university medical centers. PATIENT(S): A total of 103 5-year-olds who were born after TESE-ICSI. INTERVENTION(S): The follow-up of the children was performed by questionnaires at birth and again at 1 year and at 4 years of age. Five-year-old children were invited for individual assessment. Behavioral performance was assessed with the use of the Child Behavior Checklist for parents and teachers. Cognitive performance was assessed with the use of the Dutch Wechsler Preschool and Primary Scale of Intelligence test, 3rd version. Motor performance was assessed with the use of the Dutch Movement Assessment Battery for Children, 2nd version. Physical development was assessed by means of physical examination and medical history. MAIN OUTCOME MEASURE(S): Behavioral, cognitive, and motor performance and physical development. RESULT(S): Eighty-nine children were completely assessed, and 14 were partially assessed at the age of 5 years. The 5-year-old cohort assessed significantly better on behavioral and cognitive performance and significantly worse on motor performance-but still in the normal range-compared with the theoretic distribution in the general population. Four children (3.8%) of the 5-year-old cohort had developmental problems/delays. Two of them were previously diagnosed with a form of autism (pervasive developmental disorder-not otherwise specified). Two children had developmental problems based on our behavioral, cognitive, and/or motor assessments. CONCLUSION(S): The long-term effects on development and health in children born after TESE-ICSI procedures seem to be reassuring.

Live birth rates after MESA or TESE in men with obstructive azoospermia: is there a difference?

STUDY QUESTION: How do live birth rates compare after intracytoplasmic sperm injection (ICSI) for men with obstructive azoospermia when using sperm derived from testicular sperm extraction (TESE) versus microsurgical epididymal sperm aspiration (MESA)? SUMMARY ANSWER: Our study suggests that proximal epididymal sperm (from MESA) result in higher live birth rates as compared with testicular sperm (from TESE) in couples where the man has obstructive azoospermia due to congenital bilateral absence of the vas deferens (CBAVD) or vasectomy. WHAT IS KNOWN ALREADY: For couples with obstructive azoospermia, MESA (epididymal sperm) and TESE (testicular sperm) have generally been assumed to be equivalent for use in ICSI. But this assumption has never been confirmed, and this view has important clinical and basic scientific consequences. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of a consecutive cohort of 374 men with obstructive azoospermia and normal spermatogenesis, who underwent IVF and ICSI using either epididymal sperm or testicular sperm in the period 2000-2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included men undergoing MESA or TESE at St. Luke's Hospital for obstructive azoospermia due to CBAVD or vasectomy. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 280 couples underwent MESA and 94 underwent TESE with ICSI. The live birth rate was 39% after MESA-ICSI and 24% after TESE-ICSI. The MESA-ICSI cycles also resulted in a significantly higher implantation rate and significantly higher clinical and ongoing pregnancy rates than the TESE-ICSI cycles. There was no significant difference in results between fresh or frozen sperm for both MESA and TESE. When adjusted for the available confounders, the odds ratio for live birth was significantly in favour of MESA-ICSI versus TESE-ICSI (OR 1.82; 95% CI 1.05-3.67). The only significant confounders were female age and ovarian reserve. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective cohort study and not a randomized clinical trial. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that some aspect of sperm maturation after the sperm leaves the testicle to enter the epididymis is required for the most optimal results, even when ICSI is used for fertilization. STUDY FUNDING/COMPETING INTERESTS: No funding was used and there are no competing interests.

Enrichment of spermatogonial stem cells from long-term cultured human testicular cells.

OBJECTIVE: To evaluate the degree of enrichment of spermatogonial stem cells (SSCs) from human testicular cell cultures by ITGA6+, HLA-/ITGA6+, GPR125+, and HLA-/GPR125+ magnetic-assisted cell sorting (MACS). DESIGN: Experimental basic science study. SETTING: Reproductive biology laboratory. PATIENT(S): Multiple samples of cryopreserved human testicular cells from two prostate cancer patients with normal spermatogenesis. INTERVENTION(S): Cultured human testicular cells subjected to four sorting strategies based on MACS and xenotransplanted to the testes of mice to determine the enrichment for SSCs. MAIN OUTCOME MEASURE(S): Enrichment for human spermatogonia and SSCs tested by expression analysis of spermatogonial markers ITGA6, GPR125, ZBTB16, UCHL1, and ID4 using quantitative real-time polymerase chain reaction (qPCR) and by xenotransplantation into the testes of mice, respectively. RESULT(S): Compared with the nonsorted cultured testicular cells, only the ITGA6+ and HLA-/GPR125+ sorted cells showed enrichment for ID4. No difference in expression of ZBTB16 and UCHL1 was observed. Xenotransplantation of the sorted cell fractions showed a 7.1-fold enrichment of SSCs with ITGA6+. CONCLUSION(S): Magnetic-assisted cell sorting of cultured human testicular cells using ITGA6 allows for enrichment of SSCs, which aids in further molecular characterization of cultured human SSCs and enhances testicular colonization upon transplantation in future clinical settings.

Massive Bleeding and Massive Transfusion.

Massive bleeding in trauma patients is a serious challenge for all clinicians, and an interdisciplinary diagnostic and therapeutic approach is warranted within a limited time frame. Massive transfusion usually is defined as the transfusion of more than 10 units of packed red blood cells (RBCs) within 24 h or a corresponding blood loss of more than 1- to 1.5-fold of the body's entire blood volume. Especially male trauma patients experience this life-threatening condition within their productive years of life. An important parameter for clinical outcome is to succeed in stopping the bleeding preferentially within the first 12 h of hospital admission. Additional coagulopathy in the initial phase is induced by trauma itself and aggravated by consumption and dilution of clotting factors. Although different aspects have to be taken into consideration when viewing at bleedings induced by trauma compared to those caused by major surgery, the basic strategy is similar. Here, we will focus on trauma-induced massive hemorrhage. Currently there are no definite, worldwide accepted algorithms for blood transfusion and strategies for optimal coagulation management. There is increasing evidence that a higher ratio of plasma and RBCs (e.g. 1:1) endorsed by platelet transfusion might result in a superior survival of patients at risk for trauma-induced coagulopathy. Several strategies have been evolved in the military environment, although not all strategies should be transferred unproven to civilian practice, e.g. the transfusion of whole blood. Several agents have been proposed to support the restoration of coagulation. Some have been used for years without any doubt on their benefit-to-risk profile, whereas great enthusiasm of other products has been discouraged by inefficacy in terms of blood transfusion requirements and mortality or significant severe side effects. This review surveys current literature on fluid resuscitation, blood transfusion, and hemostatic agents currently used during massive hemorrhage in order to optimize patients' blood and coagulation management in emergency medical aid.