Intracytoplasmic sperm injection in partial globozoospermia.

OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI) in patient couples where the male partner has partial globozoospermia with the outcome in a general ICSI population. DESIGN: Case-control study. SETTING: Center for Reproductive Medicine, Radboud University Nijmegen Medical Center, the Netherlands, a tertiary referral center. PATIENT(S): Between 1997 and 2005, 42 couples were identified in which the male presented with partial globozoospermia; 27 couples treated with ICSI were matched with 263 control couples from a general ICSI population regarding female age and year of first ICSI cycle. INTERVENTION(S): One ICSI treatment (1-10 ICSI cycles). MAIN OUTCOME MEASURE(S): Live birth rate after one ICSI treatment (1-10 ICSI cycles). RESULT(S): In the partial globozoospermia group, the live birth rate was 66.7% compared with 50.0% in the control group. In partial globozoospermia, three out of 21 pregnancies ended in a miscarriage, one major birth defect occurred, and one pregnancy ended in a neonatal death due to sepsis in a premature child, compared with four stillborn in the control group. CONCLUSION(S): ICSI is an effective treatment in couples that failed to conceive spontaneously within 1 year combined with male infertility due to partial globozoospermia. The fertilization rates and the live birth rates in this specific group did not differ from those of the general ICSI population.

Prospects for delivery of recombinant angiostatin by cell-encapsulation therapy.

Implantation of encapsulated nonautologous cells that have been genetically modified to secrete proteins with tumor suppressor properties represents an alternative nonviral strategy to cancer gene therapy. We report an approach to raise the yield of recombinant proteins from encapsulated cells substantially. We hypothesized that by optimizing the encapsulation procedure, the production efficacy from the encapsulated cells could be increased. HEK 293 EBNA cells were genetically engineered to produce angiostatin. Encapsulation was performed by varying bead size, cellular density, homogeneity, and ion composition of the gel. The morphology and viability of the cells and the release of angiostatin were studied. Computer software was developed for three-dimensional imaging and quantification of cell viability. Angiostatin production was assessed at 3, 6, and 11 weeks using enzyme-linked immunosorbent assay (ELISA). Inhomogeneous gels facilitated cell growth and viability. The most efficient inhomogeneous microcapsules were generated by reducing the size and cellular density of the beads. The viability and the production of angiostatin were 3 to 5 times higher than in the homogeneous capsules. Significant amounts of viable cells were present in both homogeneous and inhomogeneous beads after 6 months of culture. The stability of the alginate matrix was greatly enhanced by gelling in the presence of barium. In conclusion, the viability and production efficacy of recombinant angiostatin from alginate-encapsulated cells can be increased considerably by optimizing the encapsulation procedure. The development of such optimized microcapsules brings cell-encapsulation therapy further towards clinical use in cancer therapy.