Sheep Postcoital Testing to Evaluate Nonhormonal Contraceptive Antibody Solution [ID 1442]

INTRODUCTION: An alternative to hormonal contraception utilizes vaginal methods, such as anti-sperm antibodies that bind and reduce progressively motile sperm (PMS). Sheep models, due to similar reproductive anatomy and size as humans, have been used for surrogate postcoital testing during development of vaginal products to evaluate potential for contraceptive efficacy before advancing to testing in humans. METHODS: Pooled semen from five prescreened human male donors was collected and evaluated for adequate motility prior to use. Ewes (n=12) were given a 1-mL dose of 3.3, 33, or 333 micrograms of proprietary antibody or phosphate-buffered saline (PBS) control solution, then mixed with 15 strokes with a test tube. After 5 minutes, 1 mL of semen was instilled for 2 minutes, mixed with five test tube strokes, and the semen/drug/vaginal secretion mixture was retrieved for microscopic examination. Progressively motile sperm were counted via video analysis for pooled and sheep samples, reported as #PMS/high powered field (hpf), and analyzed with ANOVA ( P <.05 significant). RESULTS: Pooled semen had 35±6 PMS/hpf. Control sheep (PBS) had 10±3 PMS/hpf. Sheep given the 3.3-, 33-, and 333-microgram doses had 3.3±2, 0.2±0.5, and 0.07±0.2 PMS/hpf, respectively. The two highest concentration solutions reduced the fraction of PMS by 98–99%. CONCLUSIONS/IMPLICATIONS: With a threshold of less than 1.0 PMS/hpf considered effective contraception in clinical studies, the 33- and 333-microgram antibody solutions showed potential for contraceptive use in this sheep PCT study. However, the solutions would require formulation into a usable product prior to advancement into human studies.