Recent advances in assisted reproductive technologies

Assisted reproductive technologies (ART) have received considerable attention, both clinically and empirically. Drs. Steptoe and Edwards removed one oocyte surgically from a woman with infertility related to tubal disease. They fertilized this oocyte in vitro and transferred the formed embryo to the woman’s uterus and achieved pregnancy and delivery. The technique of in vitro fertilization (IVF) and embryo transfer (ET) quickly became widely utilized for other causes of infertility as well as for tubal disease. In the last 5 years there has been a number of new developments that are reviewed in this article. The most important and now widely practiced technology has been direct intracytoplasmic injection (ICSI) of the husband’s sperm into the wife’s oocyte. This was developed for treatment of infertility related to low sperm count. Subsequently it was shown that sperm can be aspirated from epididymis or found in testicular biopsy in obstructive azoospermia. Another promising development is in vitro maturation (IVM) of immature oocytes. This has the potential of avoiding ovarian hyperstimulation, which can be uncomfortable and occasionally dangerous. Some oocytes are unable to fertilize and/or develop into normal embryos. It may be possible that the problem is with the machinery of cytoplasm of the oocyte. Therefore cytoplasmic transfer from a normal oocyte to an abnormal oocyte may overcome the problem. Infertile couples may be faced with many psychological problems that become even more complex with various treatments. Whereas donation of oocytes or embryos can be technically quite simple, there are many psychological issues involved. As can be gathered from aforementioned discussions, the treatments developed for infertility appear to be somewhat illogical and in the style of “shot gun therapy.” In the field of infertility, as in other areas of medicine, it is of paramount importance to know the details of disease mechanisms. This in turn will allow specific and logical treatments to be developed.     

Highlights of the Urethral Dysfunction sessions at the Society for Urodynamics and Female Urology

This paper reports on the currently available information regarding urethral dysfunction as presented during the scientific session of the 2006 Society for Urodynamics and Female Urology meeting in Atlanta, GA. Anatomic studies of the urethral sphincter complex contribute to our understanding of the continence mechanism, particularly as it relates to sex differences and the effect of androgens. It is important to understand biomechanical concepts of load and stress as they relate to the demonstration of incontinence on urodynamic studies. Urethral imaging complements our ability to accurately diagnose clinical problems. The pharmacologic components of urethral pressure are also discussed. Continued advances in our understanding of urethral dysfunction will guide improved diagnosis and treatment of these disorders.     

Evidence-based multidisciplinary practice: improving the safety and standards of male bladder catheterization.

A series of nursing care variances related to the procedure of catheterizing male patients stimulated an evidence-based practice project designed to define best practice for the technique of inserting male catheters. Results indicate current nursing knowledge may be inadequate.     

Integrin-targeted nanocomplexes for tumour specific delivery and therapy by systemic administration

Nanoparticle formulations offer opportunities for tumour delivery of therapeutic reagents. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a PEGylated, endosomally-cleavable lipid and an RGD integrin-targeting, endosomally-cleavable peptide. Nancomplexes self-assemble on mixing with plasmid DNA to produce nanoparticles of about 100 nm. The environmentally-sensitive linkers promote intracellular disassembly and release of the DNA. RTNs carrying luciferase genes were administered intravenously to mice carrying subcutaneous neuroblastoma tumours. Luciferase expression was much higher in tumours than in liver, spleen and lungs while plasmid biodistribution studies supported the expression data. Transfection in tumours was enhanced two-fold by integrin-targeting peptides compared to non-targeted nanocomplexes. RTNs containing the interleukin-2 (IL-2) and IL-12 genes were administered intravenously with seven doses at 48 h intervals and tumour growth monitored. Tumours from treated animals were approximately 75% smaller on day 11 compared with RTNs containing control plasmids with one third of treated mice surviving long-term. Extensive leukocyte infiltration, decreased vascularization and increased necrotic areas were observed in the tumours from IL2/IL12 treated animals. Splenocytes from re-challenged mice displayed enhanced IL-2 production following Neuro-2A co-culture, which, combined with infiltration studies, suggested a cytotoxic T cell-mediated9 tumour-rejection process. The integrin-targeted RTN formulation may have broader applications in the further development of cancer therapeutics.