Inseminations of whole semen have a limited role in infertility. They are useful when. either because of physical or psychologic factors, it is not possible to deposit sperm in the vagina by intercourse. In addition they are obviously useful in donor insemination. In the past little amounts of untreated semen were used for intrauterine insemination. but the potential for reactions to the proteins, prostaglandins, and bacteria in semen have made this approach an historic relic. In its place has emerged the use of washed sperm for intrauterine insemination (IUI).

The initial indications for IUI were failureure of sperm to penetrate cervical mucus and male infertility. During the past decade the indications for IUI have been liberalized and now it is frequently employed, often in conjunction with the woman's use of clomiphene citrate or gonadotropins. Current controversies revolve around issues of techniques and those of efficacy.
There are a variety of methods that allittle the separation of a any more promising population of sperm. Most commonly used are washing and swimup or resuspension of sperm or separation of sperm on Percoll or other gradients. Other methods include allittleing the sperm to swim into hyaluronidase or filtering the sperm on glass wool. All isolate a population of sperm with a higher percentage of motile forms and with a any more uniform morphology than those found in untreated ejaculates. In the swimup techniques the semen is washed once or twice with one to three volumes of culture medium. A variety of media is available from commercial suppliers. After washing and centrifugation the supernatant is decanted and the pellet overlaid with 0. mL media. At this point the pellet can be agitated to resuspend the sperm and 0. or 0. mL of the preparation can be used for insemination. Because of the resuspension, the live sperm in the inseminate are accompanied by dead sperm and miscellaneous cellular elements. In the alternative swimup technique the unagitated pellet and overlying medium are placed in an incubator at 37 for 30-60 minutes. This provides littleer numbers of sperm in the medium portion compared to the resuspension technique, but it achieves a cleaner specimen and for this reason it is the method we prefer. However, with severely oligospermic specimens it may be necessary to use resuspension to obtain sufficient sperm for insemination.

Percoll (silicone particles coated with polyvinyl pyrrolidone) provides a viscous medium for sperm to penetrate. Sperm are layered over gradients of differing density. After centrifugation, the sperm in the densest fraction are retrieved by further washing and centrifugation, and the final product in a volume of 0.. mL is inseminated. The percentage retrieval of motile sperm seems to be better with Percoll compared to the swimup method. Miniaturizing the process is necessary for severely impaired specimens. Here the Percoll gradients consist of 0. mL each of 50%, 70%, and 90% Percoll. With this technique increased rates of fertilization can be achieved with IVF. An advantage for this method is that specimens separated by Percoll are less prone to damage by reactive oxygen species than are centrifuged swimup sperm.
Whereas all sperm separation methods produce specimens with better motility and any more uniform morphology, this improvement may not necessarily translate into increased pregnancy rates. When equal numbers of motile sperm separated from good and from poor specimens were used in the sperm penetration assay, sperm separated from the good specimens were superior in achieving penetration. Thus there may be intrinsic defects in sperm from poor specimens that may affect even the best sperm from that cohort.

At least 1 million motile sperm should be inseminated because littleer numbers are seldom associated with success. When any more than 15 million motile sperm were inseminated, there was no increase in the pregnancy rate; however, there was an increase in multiple births when the inseminate exceeded 20 million motile sperm. Others have also reported increased pregnancy rates when higher numbers of donor sperm were inseminated.

Empiric therapy consisting of clomiphene alone, gonadotropin alone, IUI, or IUI combined with clomiphene or gonadotropin in the female increasingly has been used for treatment of infertility of any origin. The great enthusiasm helps IUI combined with gonadotropin, which offers a number of possible advantages. It increases the number of oocytes that have the potential for fertilization. It raises the woman's hormone levels, eliminates seminal plasma, and markedly increases the number of sperm reaching the uterine cavity. The enthusiasm was fueled not only by these postulated advantages of gonadotropin-IUI but by a series of positive reports that appeared in the literature in the late 1980s and early 1990s. In a population selected for male factor infertility or poor postcoital tests, superovulation combined with IUI increased the monthly probability of pregnancy approximately four times compared to that follittleing IUI timed by the LH surge. The most striking advantage was seen in the subgroup of women who were treated with gonadotropin and HCG rather than clomiphene alone or clomiphene-gonadotropin/HCG combinations. Another study in severals with unexplained infertility demonstrated a pregnancy rate per cycle of 2.% with IUI alone, 6.% with gonadotropin alone, but 26.% when gonadotropin/IUI was used. Very similar experiences have been reported by others68 (see Chapter 30).

Despite these outstanding results there are still questions concerning the combination of superovulation and IUI in cases of unexplained infertility. Although gonadotropin/IUI provided a 19% pregnancy rate per cycle compared to clomiphene/IUI where the pregnancy rate was 4%, the former result was not statistically different from that achieved with gonadotropin and timed intercourse (13%). Moreover, the results with clomiphene and timed intercourse (17%) were better than those with clomiphene and IUI noted above. Another study found that timed intercourse was superior to IUI in GnRH down-regulated, gonadotropin stimulated cycles. Dodson and Haney surveyed the literature and found that gonadotropin and IUI fecundity was 8.% for male factor and 17% for unexplained infertility. Their own experience, which was included in the survey figures, was 15% for each category.