Congenital absence of the vas deferens (CAV), failed vasoepididymostomy, and all irreparable obstructions were once very frustrating conditions, because these patients have normal spermatogenesis, but were previously untreatable (Silber SJ, Ord T, Balmaceda J et al (1990) New England Journal of Medicine 323: 1788-1792). Microsurgical epididymal sperm aspiration (MESA) together with in vitro fertilization was introduced in 1985 and in 1988 to treat these cases, but only modest success was achieved (Temple-Smith PD, Southwick GJ, Yates CA et al (1985) Journal of In Vitro Fertilization and Embryo Transfer 2: 119-122; Silber SJ, Asch R, Balmaceda J et al (1988) Fertility and Sterility 500: 525-528; Silber SJ, Ord T, Balmaceda J et al (1990) New England Journal of Medicine 323: 1788-1792). It is very difficult to predict in which cases epididymal sperm will fertilize and in which cases it will not. The reason for this problem may be either sperm maturation defects that are poorly defined or senescent and pathological changes caused by the obstruction. Thus, intracytoplasmic sperm injection (ICSI) became necessary to achieve consistently good results with MESA. The only factor in these couples which affected success had nothing to do with the sperm origin or quality but rather was simply the age and ovarian reserve of the wife. Clearly, whether sperm was from the epididymis or the testis, frozen or fresh, or whether the male had CAV, or irreparable obstruction from a variety of other causes, made no meaningful difference. The cystic fibrosis genotype, the sperm morphology and the quality of motility had no impact. Furthermore, the only factor in the wife that mattered was her age. It is crucial to screen for CF in both the husband with CAV and also his wife. If the wife is negative for any of the 36 common CF mutations, we feel that it is quite safe to perform MESA-ICSI on the couple. The chances of a male offspring's having CAV are very remote, and the chances of the child's having cystic fibrosis are probably less than in a normal, unscreened population. However, if the wife turns out to be a CF carrier herself (4% incidence in the general population), the couple can still undergo MESA-ICSI, but pre-implantation embryo diagnosis would then be mandatory. We have published the first case of successful pre-implantation embryo diagnosis in a CAV-MESA case in which both partners were carriers of the delta F508 mutation (Liu J, Lissens W, Silber SJ et al (1994) Journal of the American Medical Association 23: 1858-1860. We require this as a routine approach whenever the female is discovered, on screening, to be a CF carrier.