Men with low hypoosmotic swelling test (HOST) scores (<50%) rarely achieve a pregnancy with intercourse or conventional intrauterine insemination (IUI) or even IVF. The defect seems to be related to a toxic factor attached to the sperm that can be transferred to the zona pellucida, which ultimately interferes with implantation. A small case series showed optimistic pregnancy outcome with treatment of the sperm with low HOST scores with chymotrypsin. However, the live pregnancy rate in 90 subsequent IUI cycles in men whose low HOST scores were improved by chymotrypsin was only 3.3%. IVF with ICSI remains the only highly effective treatment of this disorder.