Sickle cell disease and infertility risks: implications for counseling and care of affected girls and women.

INTRODUCTION: Sickle cell disease (SCD), its treatments and cures present infertility risks. Fertility counseling is broadly indicated for affected girls and women and fertility preservation may appeal to some. Several streams of evidence suggest that the reproductive lifespan of women with SCD is reduced. Pregnancy is associated with high miscarriage rates. There are enduring questions about the effects of highly effective hydroxyurea treatment on female fertility. Current conditioning regimens for gene therapy or hematopoietic stem cell transplant are gonadotoxic. Fertility preservation methods exist as non-experimental standards of care for girls and women. Clinicians are challenged to overcome multifactorial barriers to incorporate fertility counseling and fertility preservation care into routine SCD care. AREAS COVERED: Here we provide a narrative review of existing evidence regarding fertility and infertility risks in girls and women with SCD and consider counseling implications of existing evidence. EXPERT OPINION: Addressing fertility for girls and women with SCD requires engaging concerns that emerge across the lifespan, acknowledging uncertainty and identifying barriers to care, some of which may be insurmountable without public policy changes. The contemporary SCD care paradigm can offer transformative SCD treatments alongside comprehensive counselling that addresses fertility risks and fertility preservation opportunities.

Severe ovarian hyperstimulation syndrome requiring recurrent large-volume paracenteses until 21 weeks' gestation: a case report.

Objective: To report a case of severe ovarian hyperstimulation syndrome (OHSS) persisting into the late second trimester of a singleton pregnancy. Design: Case report. Setting: Academic tertiary care center. Patients: A 29-year-old woman with severe OHSS after fresh embryo transfer after controlled ovarian hyperstimulation requiring intervention until 21 weeks' gestation in a singleton pregnancy. Interventions: Thorough evaluation of an unusual case of severe OHSS and medical/procedural management of its sequelae in the setting of ongoing pregnancy. Main Outcome Measuress: The clinical development of severe OHSS during pregnancy and its effect on pregnancy outcomes. Results: Severe OHSS persisted until 21 weeks' gestation with reaccumulating ascitic fluid, which impacted pregnancy outcomes. Conclusions: Clinicians should be aware of the risk of severe OHSS and its possible effect on pregnancy outcomes beyond the first trimester.

Experimental investigation into the effect of compliance of a mock aorta on cardiac performance.

Demand for heart transplants far exceeds supply of donated organs. This is attributed to the high percentage of donor hearts that are discarded and to the narrow six-hour time window currently available for transplantation. Ex-vivo heart perfusion (EVHP) provides the opportunity for resuscitation of damaged organs and extended transplantation time window by enabling functional assessment of the hearts in a near-physiologic state. Present work investigates the fluid mechanics of the ex-vivo flow loop and corresponding impact on cardiac performance. A mechanical flow loop is developed that is analogous to the region of the EVHP system that mimics in-vivo systemic circulation, including the body's largest and most compliant artery, the aorta. This investigation is focused on determining the effect of mock aortic tubing compliance on pump performance. A custom-made silicone mock aorta was developed to simulate a range of in-vivo conditions and a physiological flow was generated using a commercial ventricular assist device (VAD). Monitored parameters, including pressure, tube distension and downstream velocity, acquired using time-resolved particle imaging velocimetry (PIV), were applied to an unsteady Bernoulli analysis of the flow in a novel way to evaluate pump performance as a proxy for cardiac workload. When compared to the rigid case, the compliant mock aorta case demonstrated healthier physiologic pressure waveforms, steadier downstream flow and reduced energetic demands on the pump. These results provide experimental verification of Windkessel theory and support the need for a compliant mock aorta in the EVHP system.

Normothermic Ex Situ Heart Perfusion in Working Mode: Assessment of Cardiac Function and Metabolism.

The current standard method for organ preservation (cold storage, CS), exposes the heart to a period of cold ischemia that limits the safe preservation time and increases the risk of adverse post-transplantation outcomes. Moreover, the static nature of CS does not allow for organ evaluation or intervention during the preservation interval. Normothermic ex situ heart perfusion (ESHP) is a novel method for preservation of the donated heart that minimizes cold ischemia by providing oxygenated, nutrient-rich perfusate to the heart. ESHP has been shown to be non-inferior to CS in the preservation of standard-criteria donor hearts and has also facilitated the clinical transplantation of the hearts donated after the circulatory determination of death. Currently, the only available clinical ESHP device perfuses the heart in an unloaded, non-working state, limiting assessments of myocardial performance. Conversely, ESHP in working mode provides the opportunity for comprehensive evaluation of cardiac performance by assessment of functional and metabolic parameters under physiologic conditions. Moreover, earlier experimental studies have suggested that ESHP in working mode may result in improved functional preservation. Here, we describe the protocol for ex situ perfusion of the heart in a large mammal (porcine) model, which is reproducible for different animal models and heart sizes. The software program in this ESHP apparatus allows for real-time and automated control of the pump speed to maintain desired aortic and left atrial pressure and evaluates a variety of functional and electrophysiological parameters with minimal need for supervision/manipulation.