David A. Schirmer

Cytokine storm in a mouse model of IgG-mediated hemolytic transfusion reactions.

Cytokines are hypothesized to play a central role in the pathophysiology of IgG-mediated hemolytic transfusion reactions (HTRs), and deeper understanding is required for improving therapy for these events. After establishing well-defined mouse models of HTRs, we tested whether cytokines were involved. Red blood cells (RBCs) from human glycophorin A transgenic (hGPA-Tg) or wild-type (WT) mice were transfused into non-Tg recipients passively immunized with monoclonal antibodies (Mabs). Only transfusions of incompatible RBCs induced IgG-mediated HTRs, exemplified by rapid clearance and hemoglobinuria. Very high plasma levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), and lower levels of tumor necrosis factor-alpha (TNF-alpha), were induced after incompatible transfusion. No significant changes in IL-10, IL-12, or interferon-gamma (IFN-gamma) levels were observed. The proinflammatory cytokines elaborated in this in vivo mouse model are also implicated in the systemic inflammatory response syndrome (SIRS) and confirm the hypothesis that cytokine storm occurs as a result of HTRs.

Fertility preservation options in transgender people: A review

Gender affirming procedures adversely affect the reproductive potential of transgender people. Thus, fertility preservation options should be discussed with all transpeople before medical and surgical transition. In transwomen, semen cryopreservation is typically straightforward and widely available at fertility centers. The optimal number of vials frozen depends on their reproductive goals and treatment options, therefore a consultation with a fertility specialist is optimal. Experimental techniques including spermatogonium stem cells (SSC) and testicular tissue preservation are technologies currently under development in prepubertal individuals but are not yet clinically available. In transmen, embryo and/or oocyte cryopreservation is currently the best option for fertility preservation. Embryo cryopreservation requires fertilization of the transman’s oocytes with a donor or partner’s sperm prior to cryopreservation, but this limits his future options for fertilizing the eggs with another partner or donor. Oocyte cryopreservation offers transmen the opportunity to preserve their fertility without committing to a male partner or sperm donor at the time of cryopreservation. Both techniques however require at least a two-week treatment course, egg retrieval under sedation and considerable cost. Ovarian tissue cryopreservation is a promising experimental method that may be performed at the same time as gender affirming surgery but is offered in only a limited amount of centers worldwide. In select places, this method may be considered for prepubertal children, adolescents, and adults when ovarian stimulation is not possible. Novel methods such as in-vitro activation of primordial follicles, in vitro maturation of immature oocytes and artificial gametes are under development and may hold promise for the future.

Early Detection of Ovarian Dysfunction by Anti-Mullerian Hormone in Adolescent and Young Adult-Aged Survivors of Childhood Cancer

PURPOSE Current guidelines recommend screening at-risk childhood cancer survivors for ovarian dysfunction using follicle-stimulating hormone (FSH). However, FSH identifies diminished ovarian reserve (DOR), a component of ovarian dysfunction, in the later stages when fertility preservation is less likely to succeed. This analysis evaluates the utility of anti-Mullerian hormone (AMH) for the assessment of DOR in adolescent and young adult (AYA)-aged survivors of childhood cancer. METHODS A retrospective chart review of 13- to 21-year-old female survivors who received gonadotoxic therapy and were ≥2 years off therapy was performed. Gonadotoxic treatments were categorized as low, moderate, or high risk for future infertility. Patients with AMH below the assays age-specific normal range were identified and stratified by FSH values (normal ≤12 mIU/mL). Prevalence of low AMH and AMH-FSH subgroups was calculated and risk factors were evaluated using logistic regression. RESULTS AMH was measured in 190 survivors who received gonadotoxic treatment; of them, 35.3% had low AMH. Among survivors who received <30 Gy cranial radiation and were not on hormone therapy (n = 141), 18.4% had normal FSH with low AMH. Stratified by future infertility risk, 10.6% of low-risk, 38.1% of moderate-risk, and 25.7% of high-risk survivors had normal FSH with low AMH (p < 0.01). Within the low-risk group, normal FSH with low AMH was significantly associated with older age at diagnosis (p = 0.02). CONCLUSION Nearly 20% of AYA-aged at-risk survivors had low AMH and normal FSH. DOR in these patients would have been missed in standard recommended surveillance practices.