Frontiers in Nonhormonal Male Contraception: A Call for Research

Abstract

This paper describes the current state of research in two little-known but promising areas of nonhormonal male contraception: vas-based methods (no-scalpel vasectomy, chemical injection, injectable plugs, the Shug, and SMA) and heat methods (simple wet heat, artificial cryptorchidism, polyester suspensories, and ultrasound). Each has a clear advantage over current contraceptives (male and female) in one or more areas of safety, effectiveness, convenience, reversibility, and avoidance of surgery. These promising methods merit more research attention and allocation of resources.

Introduction

We speak of a "contraceptive supermarket" for women - the concept that since no one method is right for everybody, a variety of methods should be available (Djerassi 1981). We argue that the pill's unsuitability for older women doesn't mean it should be kept from younger women; that the diaphragm is right for some women despite its messiness and restriction of spontaneity; that the sponge's relatively low effectiveness rate doesn't mean it should be taken off the shelf.>

But when we think about contraceptive availability this way and what contraceptive supermarket is available to men, the answer is that only three purely male methods exist - withdrawal, the condom, and vasectomy (male sterilization). This contrasts with the list for women- the diaphragm, the sponge, IUDs, the pill, cervical caps, "morning after" pills, Norplant, Depo Provera, natural methods, ovulation detectors, the female condom, foams, jellies, suppositories, sterilization, and more (Hatcher et al. 1990, Chap. 8). And when we consider that of the three male methods withdrawal has low effectiveness, the condom faces psychological resistance and a 3-15% failure rate, and vasectomy is not reliably reversible (Engelmann et al. 1990, Hargreave 1992), the selection for men seems paltry indeed.

One common argument against providing a male contraceptive supermarket is that there is little expressed demand among the men of our society (Corea 1985, Chap. 9). However, similar statements could have been made thirty years ago about women and the pill. As seen with the introduction of the pill, the availability of a convenient method can create unprecedented demand. For example, extensive studies around the world have shown that improved vasectomy service in a particular location doubles, triples, or even multiplies exponentially the number of men who request the service as word gets out (Liskin et al. 1992). Regarding new methods, a short article in Ms. (Lissner 1992) prompted over 150 letters – half from men – and multiple additional articles in other magazines and newspapers.

Furthermore, many men are already using male contraception in the form of vasectomy, both in the United States and elsewhere. Currently 5% of the world's married couples rely on vasectomy, and the percentage of contraceptive-using married couples using vasectomy goes as high as 13-15% in Korea, Australia and the Netherlands, 17% in the United States and Great Britain, 31% in New Zealand, and 41% in Nepal (Liskin et al. 1992). Clearly demand can be high for even the far from ideal methods of today.

Men have many reasons to want improved contraceptives, not the least of which is self-determination. In industrialized countries, many men seek to limit their fertility until children are desired, which can often be more than ten years after sexual maturity (Gross 1993). In the world as a whole, more than 500 million couples want to limit their fertility, temporarily or permanently, but are unable to do so (Mahler 1992). New contraceptives must be developed which, together with improved delivery systems, will meet this need.

An additional reason to create a better male contraceptive supermarket is that doing so augments the choices available to women. Women in relationships with men have more contraceptive options when their partners can also take responsibility. With easy and safe male methods, their partners would have that option. This increased ability to control reproduction and space children can substantially improve women's and children's health, survival rates and economic status (World Bank 1984, 87; Potts & Thapa 1991). Such ability may also help reduce the pressure to push unsuitable and unsafe contraceptives in the name of population stabilization.

If a male contraceptive supermarket is clearly a good thing, the difficult question is how to create one. Most researchers and funding sources believe that the only new male contraceptive on the horizon is the "male pill," which would take years to formulate and years to approve (Djerassi 1981, Chap. 5). A recent example of work on a "male pill" is the discovery that RU486 has an effect on sperm (Yang et al. 1994). However, oral preparations, even when they are not hormonal, often are toxic and require years of research in the attempt to isolate a nontoxic part or variant. Gossypol, still researched in the search for a "male pill," is an example of this. Male hormonal contraceptives, moreover, have many of the same complex effects as female hormonal preparations. Partly because of this drawback, relatively little effort has been put into male contraception (Atkinson et al. 1985, Mastroianni et al. 1990).

However, there are other possibilites. They are not well known, and most people who know of them assume that they are not well researched. But after more than seventy years of isolated pieces of research and related discoveries, the evidence has begun to build.

This paper will introduce these methods, describe some of their history, and present the current state of research. Many methods are surprisingly viable with only small difficulties remaining. In view of the enormous technological progress made by our society in the last few decades, these comparatively modest challenges should provoke interest and effort in the scientific community. The methods will be divided into two types: vas-based methods (no-scalpel vasectomy, chemical injection, injectable plugs, the Shug, and SMA) and heat methods (simple wet heat, artificial cryptorchidism, polyester suspensories, and ultrasound).

Vas-based Methods

Vas-based methods rely on cutting, blocking or otherwise limiting fertility in the vas deferens, the passage through which sperm travel from the epididymis (where they mature) to the penis.

Vasectomy, currently the main vas-based method in use, is an important worldwide method of male contraception, as described earlier. Many researchers understand that improved vasectomy would have a huge market. Exactly how large is not known, although studies about tubal sterilization in women show that the availability of safe and sure reversal would double the percentage of women who consider sterilization and that a non-surgical procedure would add another 5-15 percent (Shain 1980). A World Health Organization study in men found that between 41 and 75 percent of men would welcome a safe, reversible, convenient nonsurgical male contraceptive which could be used separately from intercourse (World Health Organizantion 1982). Clearly such changes would have an enormous impact on worldwide contraceptive patterns.

Despite what seems to be a clear need for and interest in research on vas-based methods, very little work has been done since 1977 (Atkinson et al. 1985; Mastroianni et al. 1990). Strong barriers to acceptance of male contraception have fallen away, but research is still proceeding at a pace consistent with the old climate. This situation is due partly to lack of funding, partly to past technical difficulties (see below), and partly to improved techniques of vasectomy reversal. Vasovasostomy (vasectomy reversal), however, still results in pregnancy in only about 55% of the cases (Hargreave 1992) and is a surgical procedure which requires skilled microsurgeons and thousands of dollars - clearly not a technique available to most men. Therefore the need for simpler vas-based methods remains great.

Researchers have long dreamed of creating new vas-based methods. In the 1970s, a variety of elaborate metal valves were created, most of which either punctured the vas (due to their inflexibility) or insufficiently prevented sperm passage (Free 1978). Most of these methods (a few of which had only minor problems) died for lack of funding or proponents. The past decade, however, has brought a new crop of advances. Although these advances may seem less flashy than the magnetic valves and biogalvanic cells of old, they show many times the promise for practical and immediate application.

An ideal male contraceptive method would have five characteristics in addition to the usual criteria of safety, efficacy, and convenience. It would be 1) easily reversible (Hargreave 1992), 2) non-surgical (Zaneveld et al. 1978; Davis 1980); 3) reversible many times, as in the valve concept (Lynne & Politano 1978); 4) reversible non-surgically (Misro et al. 1979); and lastly, 5) non-occlusive. Vas occlusion (such as in vasectomy) has been associated with antibodies to sperm and the formation of sperm granulomas (inflammatory reactions to sperm leakage from the reproductive tract into surrounding tissue). Granulomas and antibodies may lower pregnancy rates after reversal (Herr et al. 1989; Urry et al. 1990).

Although only one of the following vas-based methods meets all of the criteria for an ideal male contraceptive, note that traditional vasectomy meets none of the five criteria. Therefore each of these methods would be an improvement over vasectomy.

Advances in Reaching the Vas Deferens

Two new methods of accessing the vas deferens have been developed:

1. No-scalpel Vasectomy.

   "The no-scalpel vasectomy technique is the way all vasectomies should be done. If a vasectomy can be accomplished with this minimal surgery, then any surgeon doing more surgery should justify why more is necessary." According to Dr. Douglas Huber, recent medical director of the Association for Voluntary Surgical Contraception, "These were the conclusions of one surgeon on the AVSC team of experts visiting [China]..." (Huber 1989, 217). No-scalpel vasectomy, originally developed in China, has been introduced in twenty countries (Martinez-Manautou et al. 1991) and is gaining worldwide recognition. It is described by Huber:

   The Chinese have been using a refined method of vasectomy that eliminates the scalpel, results in fewer hematomas, and leaves a much smaller wound than conventional techniques used in other countries. The [no-scalpel vasectomy] has been performed for 4-8 million men in Sichuan Province since its introduction in 1974. After application of local anesthesia, a specially designed vas fixing forceps encircles and firmly secures the vas without penetrating the skin. A curved hemostat with sharpened points is used to puncture the skin and vas sheath and stretch a small opening in the scrotum. The vas is lifted out and occluded as in other vasectomy techiques. This same midline puncture site is used to deliver the other vas in an almost bloodless procedure. The first [no-scalpel vasectomy] training outside China took place in November 1986 in Bangkok. Through May 1987, approximately 1,500 [no-scalpel vasectomies] were performed in Thailand, Sri Lanka, Nepal, and the US. Each surgeon reported a significant reduction in bleeding from the wound. The client response is favorable, the elimination of the scalpel and the smaller wound apparently being important to men in these countries just as in China. (Huber 1987, 176)

   Although it is a new technique and requires skill and training (even experienced surgeons require 15-20 supervised procedures before gaining proficiency), no-scalpel vasectomy is ultimately faster and safer than traditional vasectomy (Nirapathpongporn et al. 1990, Li et al. 1991). Because it is also "semi-surgical," rather than "surgical," it results in fewer complications and is more to men's liking. These advantages are expected to increase vasectomy's popularity (Antarsh 1988, Li et al. 1991). This is important for such a widely-used method of contraception. Utilization of no-scalpel vasectomy is also expected to increase with the publication of an issue of Johns Hopkins University's Population Reports on the subject (Liskin et al. 1992). Population Reports have broad impact in both more-industrialized and less-industrialized countries.

   The no-scalpel technique can be either a way to access the vas deferens in order to sever it (vasectomy) or a way to access the vas deferens in order to limit fertility by other means, such as chemical injection, insertion of plugs, or injection of a temporary fertility-limiting agent. Discussed here as an aid to vasectomy, it should immediately replace the standard vasectomy procedure as fast as training is available. Its use to access the vas for other fertility-limiting procedures is discussed later in this paper.

2. Percutaneous Injection. While the no-scalpel technique is a semi-surgical method of accessing the vas, percutaneous (through the skin) injection is completely nonsurgical. It is thus less threatening and less risky than even the no-scalpel method (Goldsmith et al. 1985b). This advantage, however, comes with a drawback: percutaneous injection is a delicate procedure, requires training and precision, and must be done exactly right.

   In percutaneous injection, the vas deferens is first secured and kept from moving around under the scrotal skin by the placement of a gentle clamp, which encircles the section of vas and skin. Once the vas is secured, a puncture needle is inserted into the vas and then replaced by an injection needle. Two tests are performed to make sure that the needle is correctly placed, and then the fertility-limiting substance is injected (Shunquiang & Jinbo 1986).

   Although the procedure is delicate and the needle must be placed accurately, percutaneous injection becomes reasonably fast (about ten minutes) with practice (Goldsmith et al. 1985b). The training is worthwhile, since besides being more appealing to men, percutaneous injection has the potential to be much more widely accepted than vasectomy in cultures with religious proscriptions against skin incisions.

   Over 600,000 percutaneous injections have been performed in China (Goldsmith et al. 1985a,b; Liu and Li 1993), the majority with sclerosing chemicals as the injectable. Some other options currently being studied around the world are neem oil injections (Upadhyay et al. 1993) and injections of tiny amounts of controlled-release gossypol (Ye et al. 1993). In the next section sclerosing chemicals (and some alternatives) are discussed.

There are four major new approaches to limiting fertility once inside the vas:

1. Permanent Chemical Injection.

   A number of substances can cause permanent sterilization by injection. Since 1964, researchers have tested at least 26 different combinations of chemicals in the vas (Davis 1980, Goldsmith et al. 1985a, Xiao 1987). The only two requirements for the chemical are that it be nontoxic and be a sclerosing agent (an agent which will produce enough scarring of the vas wall to block the vas). One American researcher is experimenting with intra-epididymal (rather than intra-vas) injections of pH-neutral zinc rather than sclerosing agents (Mason 1992), but until this research is more accepted most attention focuses on vas-based injections.

   Chinese researchers have performed vas-based chemical sterilization with a combination of carbolic acid and n-butyl alpha cyanoacrylate in over 500,000 men with resultant azoospermia in 96 percent of cases (Xiao 1987). A World Health Organization (WHO) test inspired by this study resulted in 90% effectiveness in the 900 men when followed up at 9-12 months (no followup was done sooner) (Pollack 1993). One advantage of these procedures is that cyanoacrylate has passed WHO toxicology tests (Pollack 1993). Obtaining funding for toxicology tests can be a major stumbling-block for new male methods.

   Permanent chemical injection is not likely to become much more reliable than the current refined Chinese technique. Whether closing the vas deferens or other vessels, a sclerosing approach generally leads to a certain number of failures (Chvapil et al. 1990). The scar tissue is not solid and compact, allowing occasional recanalization. However, despite this 4% failure rate, it appears that permanent chemical sterilization with the Chinese technique may be a valuable nonsurgical addition to the contraceptive supermarket.

2. Injectable Plugs.

   Injectable plugs are designed for one-time reversibility. They are ideal for men who believe they want permanent sterilization but would like the possibility of reversal in case of death of a child or some other unforeseen circumstance.

   One promising new lead involves a hydrogel material already approved for other medical uses (Carroll et al. 1993). Another promising lead for a plug is, unfortunately, not being pursued partly because it is not known how long the material remains stable in the body and nobody has done the necessary study to determine the answer (Chvapil et al. 1990). This leaves most plug research in China. In China over 512,000 men have received injectable plugs, which involve the same procedure as chemical injection, except that instead of a sclerosing chemical, polyurethane or silicone is injected and hardens to form a plug.

   Originally plugs used in China were made of polyurethane. Tests showed a 98% effectiveness rate, and all the men who have had their plugs removed for at least four years have fathered children, most within the first year (Shunquiang & Jinbo 1986; Zhao 1990, Zhao et al. 1992a).

   Different researchers in China also report 96% azoospermia (absence of live sperm) in their study of 53 men. However, this took two years: only 85% of the men were azoospermic after one year (Chen et al. 1992). These researchers identified that taking extra precautions to create properly-shaped plugs would have increased both the efficacy and sperm suppression rate in their study, as the 74% of subjects who had regularly-shaped plugs had 100% azoospermia at 18 months. Furthermore, if injectable plugs provide long-term protection, a delay should not be a problem, since plugs can be combined with short-term methods such as SMA (described later in this paper) to provide complete protection.

   Encouraged by preliminary results, in 1991 the World Health Organization started trials in ten men but with plugs made of silicone, which has a stronger safety record and would be accepted outside of China (Nullis 1991, Grubb 1991). Silicone provided azoospermia in all men within 5-9 months (Zhao 1992b).

   Injectable plugs seem reliably reversible but, like chemical injection, slightly less effective than vasectomy (96 to 100% in 5-18 months instead of 99.9% in 6-10 weeks). This tradeoff will appeal to some men but not others. Availability around the world would allow individuals to decide what best meets their needs.

3. The Shug.

   The "Shug" (short for silicone plug) is a non-injectable plug alternative. Its main advantage over injectable plugs is its double design, which gives it the potential to be more leak-free. Composed of two silicone plugs with nylon tails to help anchor the plugs to the vas, the Shug can be inserted into the vas deferens using the no-scalpel method. Like injectable plugs, it results in reversible sterilization. Test monkeys have shown nearly full return of fertility after seven months of Shug use (Zaneveld et al. 1988). Arguably, however, this is not enough time for an immune reaction to sperm to develop. Since immune reactions tend to lower slightly the chances of reversibility, long-term testing will be an important step in Shug development.

   The Shug's double design means that any sperm which leak past the first plug are likely to stay in the space between the plugs rather than leak past the second plug. This important principle could be applied to injectable plugs; double injectable plugs could be more reliable than single ones (Hargreave 1992).

   The Shug has recently undergone clinical trials. After researchers found about a 97 percent decrease in motile sperm count in the men studied, they subsequently decided that a properly sized Shug would be 2-4 times larger than the ones they used and repeated the trials with larger, softer devices (Zaneveld 1990,1991). Of the six men in this trial (begun in September 1992), four men showed zero sperm counts a month after implantation and two men showed only a few sperm, all dead (Zaneveld 1992). According to the researcher, everything was easier this time with the new plugs. Further trials continue to refine the device.

   If test results remain positive, the Shug could replace many standard vasectomies. In such a use, it could remain in place for a man's whole adult lifetime. Although the prospect of testing for safety for such long term use may seem daunting, this problem, which incidentally applies to most contraceptive methods, can be circumvented. Preliminary testing methods for male contraceptives are quite developed (Lee & Russell 1985, Marks 1985). Later, when human trials begin, use of the method can be time-limited as was done initially with the pill (Djerassi 1988). For example, a man can be told that the Shug has been tested by volunteer men for only eight years and that it is approved for three-year use. After three years, he will be told that he may safely use it for another three years. This approach can continue as long as the volunteers' experience remains positive. If any problems turn up, men can have their old plugs removed, thus avoiding health danger.

   Although the Shug's only advantage over no-scalpel vasectomy is increased reversibility, this is a big advantage which would be an attractive feature to many men. Understandably, funders have taken a "wait and see" attitude as the Shug goes through various modifications. However, continued positive results should lead to broadened and immediate research support.

4. S. M. A.

   SMA, a temporary means of contraception to be used with either the percutaneous or no-scalpel technique, uses the polymer stryrene maleic anhydride. When injected into the vas deferens, this polymer lowers the pH of the vas deferens enough to kill sperm passing through. To achieve the initial effect, just enough SMA is injected to coat the vas, not block it. The polymer immediately attaches itself to the walls of the vas in a thin film and then kills the sperm passing by it instead of blocking all sperm passage. Because it kills passing sperm and (depending on dosage) does not necessarily block the vas, this method is not occlusive and keeps the vas in an essentially undamaged and natural state.

   Fertility can be restored at any time. Since the polymer remains primarily whole, it can be flushed out at any time by an injection of dimethyl sulfoxide (DMSO), a bioacceptable solvent in the small quantities necessary (Rubin 1983). Thus fertility can be limited by one simple injection or restored by another (Misro et al. 1979). Alternatively, since the polymer itself dissolves very slowly in the process, fertility can be returned by just allowing the SMA to dissolve. Depending on the dosage administered, the time can be set anywhere from three months to five years (Guha et al. 1990). This method is thus ideal for child-spacing, for young men who are having children later, and for a wide variety of other men.

   SMA can be injected either percutaneously or by exposing the vas with the no-scalpel method (Sethi et al. 1991). Thus the procedure can be semi-surgical or completely non-surgical, depending on the training of the physician.

   This method has been completely safe and effective in fifteen years of rat and monkey trials (Misro et al. 1979; Guha et al. 1985, 1990; Sethi et al. 1989, 1990a,b,c, 1991, 1992). From recent studies that tested SMA's length of action in monkeys, its reversibility in rats, its teratogenic potential in rabbits, and its toxicity in rats and monkeys, results show excellent effectiveness and reversibility and no toxicity or teratogenicity (potential to cause birth defects). Results of a test on 38 men have recently been released (Guha et al. 1993). The only question remaining regarding SMA is how long it remains stable within the body, and Dr. Henry Gablenick at the U.S. Contraceptive Research and Development Program (CONRAD) has agreed to test this starting in early 1994 (Gablenick 1993). SMA's level of stability within the body (as opposed to breaking down into its components) is necessary for it to be safe for men.

   The literature reports nothing negative or discouraging about this method. As described above, it meets the five criteria. If it continues to prove safe and pass long-term tests, it appears to be THE most promising vas method to date.

Heat Methods

The deleterious effect of heat on male fertility has been known since the time of Hippocrates (Adams 1939, 312). Much as aspirin was "discovered" in the 1800s from a bark that Native Americans had long been accustomed to chewing to relieve pain, heat methods are now being "discovered" as the newest method of male contraception.>

These methods derive their effectiveness from the simple fact that the testes must be several degrees cooler than normal body temperature in order to maintain proper spermatogenesis (Fukui 1923; Moore & Oslund 1923; Watanabe 1959; Rock & Robinson 1965). One biological advantage for this has been hypothesized. Since men with high fevers are infertile until they are well again (Kandeel & Swerdloff 1988), newborns will then be more likely to have healthy fathers, thus increasing infant survival rate.

The body conveniently provides cooling by enclosing the testes in the scrotum. The scrotum performs a twofold function by keeping the testes outside the body wall and by creating a heat exchange, much like the one in the coils of a modern refrigerator, between incoming and outgoing blood vessels (Kandeel & Swerdloff 1988). When this twofold function is impeded by the wearing of tight jockey shorts (as many advice columnists have warned their readers), by high environmental temperatures, or by one of the four methods presented here, fertility will be impaired.

Heat methods do not usually produce azoospermia (absence of live sperm). If heat were a hormonal method such as testosterone injections, this would be a problem, since men receiving testosterone injections can have a very low sperm count but with very active sperm (Wallace et al. 1992). However, heat methods are different. Along with reducing count, heat reduces ability to fertilize. This is an important factor to remember for researchers who are accustomed to using azoospermia as their only acceptable goal.

All of the following contraceptive methods (with the exception of permanent ultrasound) are easily reversible, non-surgical, reversible non-surgically, reversible multiple times, and non-occlusive. Therefore, discussion will focus mainly on safety, efficacy and convenience, with an occasional note on psychological and economic factors.

Simple Wet Heat

Simple wet heat in the form of hot water, which is inexpensive and available to everyone, was the first contraceptive heat method discovered by the scientific community. In 1946 Dr. M. Voegeli, after more than ten years of experimentation with nine male volunteers, reported on this method. Although time-consuming, the method was perfectly effective and resulted in normal offspring after cessation (Corea 1985, Chap. 9).

Voegeli's program for temporary sterilization is as follows: "A man sits in a [shallow or testes-only] bath of 116 degrees Fahrenheit for forty-five minutes daily for three weeks. Six months of sterility results, after which normal fertility returns. For longer sterility, the treatment is repeated" (Corea 1985, 179). Although some men could support temperatures up to 125 degrees, water at 116 degrees Fahrenheit was found to reliably produce at least six months of sterility (Voegeli 1956).

Voegeli, a Swiss doctor practicing in India, taught the method to Indian men during famines between 1930 and 1950 (Segal 1962, 347). During that twenty-year period the doctor reported no substantial adverse side affects (Voegeli 1956).

The simple wet heat method in use today is not substantially different from what Voegeli developed in 1921, although various alternate combinations of temperature, time and heat source have been studied. More research needs to be done in this area. For example, hot packs or heating pads may work instead of hot water, and treatment at a lower temperature with a booster treatment every three weeks may be effective (Kandeel & Swerdloff 1988). Sun-baked rocks can even be used in areas where fuel and water are scarce and gathering them places a significant strain on women. In areas with higher incomes or with government support, men can have their infertility confirmed with a sperm count check.

Some might consider Voegeli's method inconvenient. However, it lasts six months, is separate from the sex act, appears to be safe and effective, and is readily available to everybody. Challenges to its implementation are that 1) not enough research funds have been directed towards this "folk" method to accumulate the huge body of evidence of safety that is required of a "new" method, and, more importantly, 2) since money can be made only from creative applications of the method (not from patenting the method itself), no large pharmaceutical firms will sponsor it (Segal 1988). Both of these problems could be solved by backing and research efforts by government and non-profit agencies.

In 1949, Voegeli began a twenty-year campaign to publicize the heat method so that, if the results of further studies were favorable, the method could be widely used (Corea 1985, Chap. 9; Robinson et al. 1968). Her attempts to publicize it were generally unsuccessful, although in 1954 the Japanese government requested the information and conducted several successful experiments (Corea 1985, Chap. 9).

Artificial Cryptorchidism

In the United States, among the few who picked up Voegeli's work were John Rock and Derek Robinson of Harvard University. Their work on the effect of insulated underwear (Robinson & Rock 1967) and hot water (Rock & Robinson 1965) on spermatogenesis forms the basis of a related new method of contraception: artificial cryptorchidism.

The idea of artificial cryptorchidism is simple. Researchers combined two pieces of information: 1) raising the temperature of the testes to body temperature (by using insulated underwear or hot water) results in subfertility (as found by Robinson, Rock and others), and 2) men with cryptorchid (undescended) or retractile testes are often infertile (Nistal & Paniagua 1984). By putting these two facts together, the pioneers in this area concluded that the testes can be raised to body temperature with less trouble than with insulated underwear by simply maintaining the testes within the inguinal canal (the tube into which retractile testes withdraw) during daytime hours (Mieusset et al. 1985).

Dr. Roger Mieusset of France, currently the chief proponent of artificial cryptorchidism, was the first to achieve effectiveness rates with artificial cryptorchidism which make it suitable for contraception (Mieusset et al. 1987). In Mieusset's method, during waking hours a man wears an under-brief which holds the testes snug against the body but doesn't tightly enclose the penis. When some of the men in his study refined the retaining underwear by adding a circle of soft fabric to keep the testes from moving out of the inguinal canal, effectiveness rates shot up. Mieusset now uses this method in his research. The new method results in an average sperm count of 3 million/ml and average motility of 15 percent (Mieusset et al. 1991), as opposed to values with the old method of 12 million/ml and 22 to 30 percent (Mieusset et al. 1987). Since infertility is generally diagnosed as under 10 million/ml sperm count and 40 to 45 percent motility (Makler 1986), and since heat also reduces sperm's ability to penetrate eggs (Paulson 1986), the desired result is clearly being achieved.

Artificial cryptorchidism meets the five criteria for an ideal male contraceptive. It also appears to be effective and relatively convenient. However, fertility return after long-term use has not been tested. This is the next crucial step. Short-term use (1-2 years) appears to allow full return of fertility: the few tests in humans have all been favorable, as have tests of other heat methods in rats, dogs and monkeys (Kandeel & Swerdloff 1988).

The final concern regarding artificial cryptorchidism is cancer. Although nearly any proposed male method can be shelved because of the suggestion that it might someday somehow cause cancer, artificial cryptorchidism presents a more logical concern. Permanent, full-time, natural cryptorchidism since childhood is associated with increased risk of testicular cancer, although causation is not known (for example, both the cryptorchidism and the cancer are quite possibly the result of a third factor) (Giwercman et al. 1988). Research must study this. Though artificial cryptorchidism is part-time rather than full-time, temporary rather than permanent, induced rather than from natural causes, and initiated in adulthood rather than childhood, these concerns will still be important to address.

On a more day-to-day level, many men fear that this method would cause "jock itch." However, Mieusset's volunteers showed no signs of jock itch. However, a true limiting factor is that about 50% of men find the sensation of retracted testes uncomfortable; the other 50% of men don't mind or don't notice the sensation (MCIP 1992). No method will appeal to all men, so this should not hold back development of artificial cryptorchidism.

As for convenience, the only modification of habits required would be for men to wear slightly different underwear: jockey shorts with an inner layer for holding the testes (Mieusset et al. 1987). Since within the past ten years women have been convinced to wear both boxer shorts and jockey shorts, the task of creating this change seems within the capabilities of the advertising establishment!

Polyester Suspensories

The newest method to join the array of heat-based choices, the polyester suspensory is similar to artificial cryptorchidism underwear but is looser and made of polyester. Its benefit over artificial cryptorchidism is the looser position of the testes, which should open its use to those men who find the inguinal position uncomfortable.

The polyester suspensory method stems from research showing polyester underwear creates a greater "electrostatic potential" (i.e. more static electricity) than either cotton or half cotton/half poly underwear (Shafik et al. 1992). Based on this, its developer concluded that the zero sperm counts obtained with polyester suspensories (i.e. a "jock strap" that holds just the testes) may be the result of both heat and static electricity across the testes (Shafik 1992a).

Many researchers reject this theory, saying that the idea of a static electricity field traveling all the way across the testes is nonsense, but agree that Dr. Shafik's findings could be the result of the intensified heat effect, since polyester retains more heat. Luckily, this question will be resolved. The United States Agency for International Development (AID), in consultation with the World Health Organization (WHO) male reproductive task force, is beginning a study of the polyester method on twelve men (Spieler 1992). Volunteers have already been selected and fitted (Wang 1994). The study is being conducted by Dr. Christina Wang at the University of California Los Angeles, a researcher whose work is well-respected and whose results are likely to hold considerable credibility. Duplication of Dr. Shafik's findings regarding effectiveness would thus set the stage for tests to determine polyester's method of action. Further tests could analyze improvements such as breathable fabric, which is expected to be just as effective as standard polyester based on preliminary results (Shafik 1992b).

Research on polyester suspensories seems likely to bring other heat methods into the limelight. Policymakers at the Agency for International Development, the World Health Organization, and the National Institutes of Health are to be commended for taking the small step necessary to get such research off the ground.

Ultrasound

Considered on technical and practical merits alone, ultrasound is one of the most promising forms of new male contraception. It is technically simple and extremely convenient in that ten minutes of ultrasound results in six months of sterility, and it requires less dedication than methods such as artificial cryptorchidism and wet heat. In contrast, the task of addressing users' (and policymakers') concerns has been more difficult than for other methods (Wilmore 1988). However, because of the efforts of one policymaker, this may be changing soon.

For ultrasound contraception, ultrasound waves (very short, inaudible sound waves) are used to heat the testes. The ultrasound waves are of the same type and intensity as those used by physical therapists to treat injuries.

To use the method, a man first sits in a special chair with his scrotum in a cup of water. In the bottom of the cup, shielded from the testes and scrotum, is an ultrasound element, which heats the water somewhat (not as hot as a hot tub) and may also, it has been found, create an ion exchange between the fluid in the seminiferous tubules and the rete testis which makes the environment in the testes inhospitable for sperm formation (Fahim et al. 1977). The method is painless. Some men even report the procedure to be pleasurable.

After five to ten minutes of ultrasound, six months of infertility results. With two treatments forty-eight hours apart, ten or more months of infertility will result (Fahim 1980). As in all heat methods, fertility returns gradually once the infertile months are over, with a surge in fertility about ten weeks later and then a gradual return to normal (Robinson & Rock 1967).

The most important priority for research is the question of whether, and how, fertility returns after multiple uses of the method (for example, after 5 to 15 years of use) (Kandeel & Swerdloff 1988). Also important is to confirm the results on safety. As was done with the pill trials, researchers should begin tests now so that longer and longer uses of ultrasound can gradually be approved (or not approved, as the case may be).

Once fertility return after long-term use is shown and safety is double-checked, the remaining barrier for ultrasound will be psychological resistance. Although all the research so far on animals and humans has had excellent results, anything that sounds like radiation worries people, including those who determine funding (Wilmore 1988). And although ultrasound was tested as a treatment for herpes simplex in women (Corea 1985, Chap.9), has been used for years to view women's fetuses, and is a regular part of physical therapy and chiropractic care for both sexes, fear and skepticism about male reproductive use prevail. Since a large and unequivocal body of information will be required in order to address this fear and skepticism, and since most work on ultrasound has been performed by one researcher, the only way for ultrasound contraception to gain acceptance is for other researchers, motivated by the overwhelmingly positive results so far, to put aside their skepticism and do the research.

Unfortunately this is not happening. Apparently the only researcher in the United States who has published extendively on ultrasound contraception is Dr. Mostafa S. Fahim, Director of the Center for Reproductive Science and Technology at the University of Missouri at Columbia. In a study of the comparative contraceptive effects of heat, ultrasound, infrared rays, and microwave rays, Fahim found ultrasound to be the safest and most effective (Fahim et al. 1975). He carried out the first definitive studies on the method of action of ultrasound and its genetic safety in future generations of animals (Fahim 1980). He holds patents on the concept of ultrasonic contraception (both for humans and for sterilizing pets) and the equipment used to accomplish it (Fahim 1988).

One would think that with so much investment in the idea, Dr. Fahim would be actively researching ultrasound and working to build the mass of data needed for its acceptance. Yet, although Dr. Fahim has collaborated with Chinese researchers on using longer and higher doses of ultrasound for permanent sterilization, in 1980 he stopped research on ultrasound as temporary contraception. One reason was limited funding. A second reason was his university's requirement that he use men with prostate cancer (who would probably have their testes surgically removed anyway) in his first human trials (Corea 1985, Chap. 9). Since it is primarily the return of fertility and not the safety of ultrasound itself that is in question (as shown by long-term use in men and women), it seems that men who are planning vasectomies could also be used as subjects, but the university would not allow this. Due to these and other similar constraints, Fahim has moved on to other areas of research.

Many researchers doubt Dr. Fahim's results, partly because they seem too good to be true, partly because of perceived problems with Dr. Fahim's methodology, and partly because a more recent study seemed to contradict the results (Urry et al. 1988). However, the more recent study, though published in 1988, was actually conducted in 1973-76 before many details of Dr. Fahim's technique were available. No matter how accurate or well respected the researchers, they conducted a study which is entirely different. Most researchers who know of ultrasound believe that it is a dead subject because of this paper; however, in reality the issue remains completely unaddressed.

Fortunately, some policymakers have begun to see this point. Though few are enthusiastic about the method even there, the U.S. Agency for International Development and possibly National Institutes of Health stand poised to duplicate one rat study (Spieler 1992). With the worldwide health issues at stake, policymakers are seeing that though they may not lavish money on ultrasound, much depends on their doing the one rat study necessary to give ultrasound a chance.

Conclusion

The five types of vas-based methods (no-scalpel vasectomy, chemical injection, injectable plugs, the Shug, and SMA) and four heat methods (simple wet heat, artificial cryptorchidism, polyester suspensories, and ultrasound) would each constitute a significant advance for male contraception. Each has a clear advantage over current contraceptives (male and female) in one or more areas of safety, effectiveness, convenience, reversibility, and avoidance of surgery. These clearly promising methods merit more research attention and allocation of more resources. First priority for research should be SMA injection, followed by artificial cryptorchidism, polyester suspensories, injectable plugs and ultrasound. However, the perfection and popularization of any of the methods discussed would significantly expand the contraceptive supermarket available to men (and thus also to women) in the years to come.

Acknowledgements

A previous version of this paper appeared in WomenWise, Spring 1991, and in Issues in Reproductive Technology I: An Anthology, 1992, Garland Publishing. Special thanks to the researchers mentioned and to everyone who supported me in this work, including Betsy Hartmann, Judy Norsigian, and Barbara Wilson for helping make this work possible.

References

Adams, F. I., translator. 1939. The genuine works of Hippocrates. Baltimore: Williams & Wilkins.

Antarsh, L. 1988. Men and their worries about vasectomy: will a new surgical technique help? AVSC News (Association for Voluntary Surgical Contraception) 26:5-6.

Atkinson, Linda E., Richard Lincoln and Jacqueline Darroch Forrest. 1985. Worldwide trends in funding for contraceptive research and evaluation. Family Planning Perspectives 17(5):196-207.

Carroll, John C., Steven D. Schwaitzberg, Angelo A. Ucci, Jr. et al. 1993. New matrix material for potential use in "reversible" vasectomy. Urology 41:34-37.

Chen, Zhen-wen, Yi-qun Gu, Xiao-wei Liang et al. 1992. Safety and efficacy of percutaneous injection of polyurethane elastomer (MPU) plugs for vas occlusion in man. International Journal of Andrology 15:468-472.

Chvapil, Milos, Thomas A. Chvapil, James A. Owen, and Diana J. Benson. 1990. Occlusion of the vas deferens in dogs with a biocompatible hydrogel solution. Journal of Reproductive Medicine 35:905-910.

Corea, Gena. 1985. The hidden malpractice. Updated ed. New York: Harper & Row.

Davis, Joseph. 1980. New methods of vas occclusion. In Research frontiers in fertility regulation, ed. Gerald Zatuchni, Miriam Labbok, and John Sciarra. Hagerstown: Harper & Row.

Djerassi, Carl. 1981. The politics of contraception. 2nd edition. San Francisco: WH Freeman & Co.

Djerassi, Carl. 1988. Personal communication.

Engelmann, U. H., P. Schramek, G. Tomamichel et al. 1990. Vasectomy reversal in central Europe: Results of questionnaire of urologists in Austria, Germany and Switzerland. Journal of Urology 143:64-67.

Fahim, Mostafa. 1980. Male fertility regulation by means of ultrasound. In Regulation of male fertility, ed. G. R. Cunningham, W. B. Schill, and E. S. E. Hafez. Boston: Martinus Nijhoff Publishers.

Fahim, Mostafa. 1988. Personal communication.

Fahim, Mostafa, Zuhal Fahim, R. Der et al. 1975. Heat in male contraception (hot water 60 degrees C., infrared, microwave, and ultrasound). Contraception 11:549-562.

Fahim, Mostafa, Zuhal Fahim, James Harman et al. 1977. Ultrasound as a new method of male contraception. Fertility and Sterility 28:823-831.

Free, Michael. 1978. Reversible intravasal devices: State of the art. In Reversal of sterilization, ed. John Sciarra, Gerald Zatuchni, and J. Joseph Spiedel. Hagerstown: Harper & Row.

Fukui, N. 1923. On a hitherto unknown action of heat ray on testicles. Japan Medical World 3:27-28.

Gablenick, Henry. 1993. Personal communication.

Giwercman, Aleksander, Jørn Müller, Niels E. Skakkebæk. 1988. Cryptorchidism and testicular neoplasia. Hormone Research 30:157-163.

Goldsmith, A., D. A. Edelman, and G. I. Zatuchni. 1985. Transcutaneous male sterilization. Research Frontiers in Fertility Regulation 3 (4):1-8.

Goldsmith, A., D. A. Edelman, and G. I. Zatuchni. 1985. Transcutaneous procedures for male sterilization. Advances in Contraception 1:355-361.

Gross, Dave. 1993. Paternity ward: An anguished appeal from the first sex for universal rights to reproductive freedom. Metro: Santa Clara Valley's Weekly Newspaper (San Jose, California) 8(45):16-18.

Guha, Sujoy K., Sneh Anand, Shirfuddin Ansari et al. 1990. Time-controlled injectable occlusion of the vas deferens. Contraception 41:323-331.

Guha, Sujoy K., Shirfuddin Ansari, Sneh Anand et al. 1985. Contraception in male monkeys by intra-vas deferens injection of a pH lowering polymer. Contraception 32:109-118.

Guha, Sujoy K., Gulshanjit Singh, Sneh Anand et al. 1993. Phase I clinical trial of an injectable contraceptive for the male. Contraception 48:367-375.

Grubb, Gary S. 1991. Experimental methods of contraception. Current Opinion in Obstetrics and Gynecology 3:491-495.

Hargreave, T. B. 1992. Towards reversible vasectomy. International Journal of Andrology 15:455-459.

Hatcher, Robert, Felicia Stewart, James Trussell et al. 1990. Contraceptive technology 1990-1992. New York: Irvington Publishers.

Herr, J. C., S. S. Howards, D. R. Spell et al. 1989. The influence of vasovasostomy on antisperm antibodies in rats. Biological Reproduction 40:353-360.

Huber, Douglas. 1987. The Chinese microvasectomy technique. Advances in Contraception 3:176.

Huber, Douglas. 1989. No-scalpel vasectomy: The transfer of a refined surgical technique from China to other countries. Advances in Contraception 5:217-218.

Kandeel, Fouad, and Ronald Swerdloff. 1988. Role of temperature in regulation of spermatogenesis and the use of heating as a method for contraception. Fertility and Sterility 49:1-23.

Lee, I. P., and L. L. Russell. 1985. Environmental chemical effects on testicular function. In Male fertility and its regulation, ed. T. J. Lobl and E. S. E. Hafez. Lancaster: MTP Press.

Li, Shunqiang, Marc Goldstein, Jinbo Zhu and Douglas Huber. 1991. The no-scalpel vasectomy. Journal of Urology 145:341-344.

Liskin, Laurie, Ellen Benoit, and Richard Blackburn. 1992. Vasectomy: New opportunities. Population Reports Series D, No. 5. Baltimore, Johns Hopkins University, Population Information Program.

Lissner, Elaine A. 1992. Contraceptive methods- For men. Ms. 2(4):75.

Liu, Xiaozhang and Shunqiang Li. 1993. Vasal sterilization in China. Contraception 48:255-265.

Lynne, Charles, and Victor Politano. 1978. Early experience with the bionyx control valve (Phaser). In Reversal of sterilization, ed. John Sciarra, Gerald Zatuchni, and J. Joseph Spiedel. Hagerstown: Harper & Row.

Mahler, Halfdan. 1992. In International Planned Parenthood Federation, Annual Report 1991-1992. London: IPPF.

Makler, Amnon. 1986. Evaluation and treatment of the infertile male. In Reproductive failure, ed. A. H. DeCherney. New York: Churchill Livingstone.

Marks, T. A. 1985. Animal tests employed to assess the effects of drugs and chemicals on reproduction. In Male fertility and its regulation, ed. T. J. Lobl and E. S. E. Hafez. Lancaster: MTP Press.

Martinez-Manautou, J., D. Hernández, F. Alarcón and S. Correu. 1991. Introduction of non-scalpel vasectomy at the Mexican Social Security Institute. Advances in Contraception 7:193-201.

Mason, Virginia. 1992. Is 'chemical vasectomy' in the offing? Contraceptive Technology Update 13(12):177-192. Available from American Health Consultants Inc., 3525 Piedmont Road Bldg. 6 Suite 400, Atlanta, GA 30305.

MCIP (Male Contraception Information Project). 1992. Available from MCIP, P.O. Box 3674, Stanford, CA 94309.

Mieusset, Roger, Louis Bujan, Arlette Mansat et al. 1987. Hyperthermia and human spermatogenesis: enhancement of the inhibitory effect obtained by 'artificial cryptorchidism'. International Journal of Andrology 10:571-580.

Mieusset, Roger, Louis Bujan, Arlette Mansat et al. 1991. Heat induced inhibition of spermatogenesis in man. In Temperature and environmental effects on the testis, ed. A. W. Zorgniotti. New York City: Plenum Press.

Mieusset, Roger, Hélène Grandjean, Arlette Mansat, and Francis Pontonnier. 1985. Inhibiting effect of artificial cryptorchidism on spermatogenesis. Fertility and Sterility 43:589-594.

Misro, Manmohan, Sujoy Guha, Harpal Singh et al. 1979. Injectable non-occlusive chemical contraception in the male -I. Contraception 20:467-473.

Moore, C.R., and R. Oslund. 1923. Experiments on the sheep testis- Cryptorchidism, vasectomy and scrotal insulation. American Journal of Physiology 67:595-607.

Mastroianni, Luigi, Peter J. Donaldson, and Thomas T. Kane, eds. 1990. Developing new contraceptives- Obstacles and opportunities. Washington, D.C.: National Academy Press.

Nirapathpongporn, Apichart, Douglas Huber, and John Krieger. 1990. No-scalpel vasectomy at the King's birthday vasectomy festival. Lancet 335:894-895.

Nistal, Manuel, and Ricardo Paniagua. 1984. Infertility in adult males with retractile testes. Fertility and Sterility 41:395-403.

Nullis, Clare. 1991. Hormonal, silicone contraceptives being tested. Associated Press release 27 June.

Paulson, R.J., B. Yee, L.M. Cummings et al. 1986. Effect of minimal heat exposure upon sperm penetration of zona-free hamster eggs. (Abstr.) Presented at the 34th annual meeting of the Pacific Coast Fertility Society, San Diego, California.

Pollack, Amy, Medical Director of Association for Voluntary Surgical Contraception (AVSC). 1993. Personal communication.

Potts, Malcolm, and Shyam Thapa. 1991. Child survival: The role of family planning. Research Triangle Park, NC: Family Health International.

Robinson, Derek, and John Rock. 1967. Intrascrotal hyperthermia induced by scrotal insulation: effect on spermatogenesis. Obstetrics and Gynecology 29:217-223.

Robinson, Derek, John Rock, and Miriam Menkin. 1968. Control of human spermatogenesis by induced changes of intrascrotal temperature. Journal of the American Medical Association 204:291-297.

Rock, John, and Derek Robinson. 1965. Effect of induced intrascrotal hyperthermia on testicular function in man. American Journal of Obstetrics and Gynecology 93:793-801.

Rubin, Lionel. 1983. Toxicologic update of dimethyl sulfoxide. Annals of the New York Academy of Sciences 411:6-10.

Segal, Sheldon. 1962. Report on research toward the control of fertility. In Research in family planning, ed. Clyde Kiser. Princeton: Princeton University Press.

Segal, Sheldon. 1988. Personal communication.

Sethi, N., R. K. Srivastava, D. Nath, and R. K. Singh. 1991. Preclinical toxicity study of a male injectable antifertility agent (styrene maleic anhydride) in rhesus monkeys, Macaca mulatta. Journal of Medical Primatology 20:89-93.

Sethi, N., R. K. Srivastava, D. Nath, and R. K. Singh. 1992. Teratological evaluation of an injectable male antifertility agent, styrene maleic anhydride, in rats. International Journal of Fertility 37:183-187.

Sethi, N., R. K. Srivastava, and R. K. Singh. 1989. Safety evaluation of a male injectable antifertility agent, styrene maleic anhydride, in rats. Contraception 39:217-226.

Sethi, N., R. K. Srivastava, and R. K. Singh. 1990a. Histological changes in the vas deferens of rats after injection of a new male antifertility agent "SMA" and its reversibility. Contraception 41:333-339.

Sethi N, R. K. Srivastava, and R. K. Singh. 1990b. Male mediated teratogenic potential evaluation of new antifertility compound SMA in rabbit (Oryctolagus cuniculus). Contraception 42:215-223.

Sethi, N., R. K. Srivastava, R. K. Singh et al. 1990c. Chronic toxicity of styrene maleic anhydride, a male contraceptive, in rhesus monkeys (Macaca mulatta). Contraception 42:337-347.

Shafik, Ahmed. 1992a. Contraceptive efficacy of polyester-induced azoospermia in normal men. Contraception 45:439-451.

Shafik, Ahmed. 1992b. Personal communication.

Shafik, Ahmed, I. H. Ibrahim, and E. M. El-Sayed. 1992. Effect of different types of textile fabric on spermatogenesis I. Electrostatic potentials generated on surface of human scrotum by wearing different types of fabric. Andrologia 24:145-147.

Shain, Rochelle. 1980. Objections to tubal sterilization: What reversibility can and cannot overcome. Contraception 22:213-225.

Shunqiang, L., and Z. Jinbo. 1986. Non-incisional sterilization with intravasal drug injection (10-year follow-up on control of blocking the length of the vas deferens). Advances in Contraception 2:241.

Spieler, Jeff, U.S. Agency for International Development. 1992. Personal communication.

Upadhyay, S.N., S. Dhawan, G.P. Talwar. 1993. Antifertility effects of neem (Azadirachta indica) oil in male rats by single intra-vas administration: an alternate approach to vasectomy. Journal of Andrology 14:275-281.

Urry, Ronald, K. A. Dougherty, S. A. Child et al. 1988. Ultrasound and spermatogenesis in the rat. Ultrasound in Medicine and Biology 14:213-217.

Urry, Ronald, J. B. Heaton, Monty H. Moore, and Richard G. Middleton. 1990. A fifteen-year study of alterations in semen quality occuring after vasectomy reversal. Fertility and Sterility 53:341-345.

Voegeli, Martha. 1956. Contraception through temporary male sterilization. Unpublished paper, available from Curator, Sophia Smith Collection, Smith College, Northampton, MA 01063.

Wallace, E. M., R. J. Aitken, and F. C. W. Wu. 1992. Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive. International Journal of Andrology 15:416-424.

Watanabe, Akira. 1959. The effect of heat on the human spermatogenesis. Kyushu Journal of Medical Science 10:101-117.

Wilmore, Laurie. 1988. The social biases affecting male contraceptive research. Unpublished paper, Program in Human Biology. Stanford, Calif.: Stanford University.

World Bank. 1984. Population change and economic development. New York: Oxford University Press.

World Health Organization Task Force on Psychosocial Research in Family Planning, Special Programme of Research, Development and Research Training in Human Reproduction. 1982. Hormonal contraception for men: Acceptability and effects on sexuality. Studies in Family Planning 13(11):328-341.

Xiao, Bilian. 1987. Chemical vas occlusion in the People's Republic of China. In Fertility Regulation Today and Tomorrow, ed. E. Diczfalusy and M. Bygdeman. New York: Raven Press.

Yang, Jing, Catherine Serres, Daniel Philibert et al. 1994. Progesterone and RU486: opposing effects on human sperm. Proceedings of the National Academy of Sciences 91:529-533.

Ye, W., G. Lu, Y. Den et al. 1993. Effect of intra-vas deferens injection of gossypol-polylactic acid on fertility and spermatogenesis in rats. Chinese Medical Sciences Journal 8:20-24.

Zaneveld, Lourens. 1990. Personal communication.

Zaneveld, Lourens. 1991. Personal communication.

Zaneveld, Lourens. 1992. Personal communication.

Zaneveld, Lourens, Stan Beyler, Gail Prins et al. 1978. Reversible vas deferens occlusion: a new device. In Reversal of sterilization, ed. John Sciarra, Gerald Zatuchni, and J. Joseph Spiedel. Hagerstown: Harper & Row.

Zaneveld, Lourens, James Burns, Stan Beyler et al. 1988. Development of a potentially reversible vas deferens occlusion device and evaluation in primates. Fertility and Sterility 49:527-533.

Zaneveld, Lourens, M. de Castro, F. Derrick et al. 1990. Clinical evaluation of a reversible vas deferens blocking device- the Shug. In Proceedings of the Third International Symposium on Contraception, 19-23 June, Heidelberg, West Germany.

Zhao, Sheng-cai. 1990. Vas deferens occlusion by percutaneous injection of polyurethane elastomer plugs: Clinical experience and reversibility. Contraception 41:453-459.

Zhao, Sheng-cai, Yi-hi Lian, Rui-chuan Yu, and Shu-ping Zhang. 1992a. Recovery of fertility after removal of polyurethane plugs from the human vas deferens occluded for up to 5 years. International Journal of Andrology 15:465-467.

Zhao, Sheng-cai, Shu-ping Zhang, and Rui-chuan Yu. 1992b. Intravasal injection of formed-in-place silicone rubber as a method of vas occlusion. International Journal of Andrology 15:460-464.

© March 8, 1994 and August 16, 1991, Elaine A. Lissner.