1 Introduction

2 Testicular suspension

One of the fields of search is the vulnerability of spermatogenesis to thermal insult^[6-9]. In a preceding experimental study on dogs^[10], the testicles of the animals were suspended in the superficial inguinal pouch for one year and then released. During testicular suspension, the semen quality deteriorated to the effect that by the 12th month, 80% of the test dogs were azoospermic. This was accompanied by a significant drop in serum testosterone, an increase of serum prolactin and the failure of dog mating to accomplish pregnancy. Three months after release of suspension, the sperm character and hormonal assay became normalized and mating produced pregnancy. Based upon these results, a simple, safe, reliable and reversible method of male contraception is developed^[11].

2.1 Technique

The procedure was carried out in 28 male volunteers. The testicles were suspended in the superficial inguinal pouch close to the scrotal neck using the technique of stitch suspension in 15 and of ball suspension in 13 subjects^[11].

2.1.1 Stitch suspension

The testicle is suspended close to the scrotal neck in the superficial inguinal pouch which lies between the external oblique and the deep layer of the superficial fascia over the inguinal canal. With the subject in the supine position, the skin at the scrotal neck is infiltrated with 5 mL 1% xylocaine. While the left hand places and holds the testicle in the described location, 2 to 300 silk stitches are taken between the skin and the tunics of the testicle so as to keep the testicle in this position.  The technique is carried out on both testicles. A suspensory sling for support is worn for 3 weeks, whereas the stitches are removed 2 weeks postoperatively. The procedure is performed on an outpatient basis.

2.1.2 Ball suspension

A suspensory sling consisting of a non-stretchable fabric is prepared separately for each subject to fit snugly around the individual scrotum. The so-called ball suspensor contains 2 compartments, each having a ball (made of textile and filled with cotton) of the size of the testicle fixed to its bottom. The ball suspensor is applied to the scrotum; the testicles are elevated to the scrotal neck. They are managed manually to lie in the superficial inguinal pouch, overlying the balls. The subjects are instructed how to apply the sling on their own. The ball suspensor is worn day and night and replaced by a fresh one only when it becomes loose or soiled.

During the 12 months of testicular suspension, the proper location of the testicles at the scrotal neck as well as their size and consistency are checked every 15 days. Rectal and intratesticular temperature and the semen are examined once a month. A testicular biopsy is taken six months after suspension. The testicle size, temperature and biopsy, and semen as well as serum testosterone, FSH, LH, and prolactin were examined before and during the testicular suspension period and after suspension release. Sexual intercourse was practised during testicular suspension and after release, but not during the first 3 months into suspension.

2.2 Suspension reversal

The ball suspension is reversed by simple discontinuation. To release stitch suspension, the skin at the scrotal neck is infiltrated with 5 mL of 1% xylocaine. Through a skin incision of 1 to 1.5 cm over the suspended testicle,  the adhesions that have developed between the testicle and the scrotal skin are cut by blunt and sharp dissection. The testicle is then drawn down to lie in the most dependent part of the scrotum. The contralateral testicle is released in the same way. The procedure is carried out at the outpatient clinic.

2.3 Results

During suspension, the sperm count dropped to severe oligozoospermia. Pregnancy did not occur. There was a significant decrease in serum testosterone and an increase in prolactin.  The mean difference between rectal and testicular temperature in the pre-suspension period was (30.2) while in post-suspension was (1.10.1) (P<0.001) Testicular biopsy showed degeneration of seminiferous tubules. Six months after testicular release, sperm count, rectal-testicular temperature difference and serum hormone levels returned to normal. The testicular biopsy showed normal spermatogenesis. Pregnancy occurred.

2.4 Comments

Many studies since the beginning of this century have established the vulnerability of spermatogenesis to relatively small increases in testicular temperature^[6-9]. Moore^[6,7], performing experimental cryptorchidism in the guinea pig, observed a complete dissolution of cells of the seminiferous tubules, except the Sertoli elements, within a period of 2 weeks. The testicles became smaller and never returned to a spermatogenic function as long as they remained in the abdomen. Re-locating the testicle, which showed residual spermatogenia, back into the scrotum resulted in the return of a normal spermatogenic function^[7-9]. Likewise, testicular grafts in rats produced spermatozoa only when attached to the inside walls of the scrotum, but failed to do so in any other locality outside the scrotum^[6]. Damage of the spermatogenic function of the testicle by artificial cryptorchidism was produced in the rat^[8,9], rabbit^[12], dog^[13], and sheep^[14] and by scrotal insulation in the ram^[15] and bull^[16]. Experiments were done to demonstrate the thermoregulatory function of the scrotum as well as the damaging effect of heat on the testicles. Thus, elevation of testicular temperature by dry^[6,17] or wet^[18,19] heat induced extensive degeneration and loss of spermatogenic tissues.

The testicle has a thermoregulatory apparatus which regulates the scrotal-rectal temperature relationship and keeps it constant in reaction to environmental temperature changes^[20-24]. Disturbance of this mechanism inhibits spermatogenesis and leads to infertility^[22,24,25].

Suspension of the testicle in the superficial inguinal pouch led to diminished spermatogenesis. This seems to be due to disordered thermoregulation resulting from 2 factors: (a) testicular fixation and (b) high testicular position.

Testicular fixation results in loss of testicular motility in reaction to changes in environmental temperature^[20-24]. The testicle loses its thermoregulatory function, and its temperature remains constant despite environmental temperature variations.

Furthermore, the location of the testicle high in the inguinal pouch close to the warm abdomen has elevated its temperature to the effect that the testicular-rectal temperature difference recorded values below normal. The constantly and significantly elevated testicular temperature seems to be responsible for the diminished spermatogenesis. The semen showed diminished sperm count and motility with an increase in abnormal sperm forms, such that by the end of the 12th month into suspension 68% of the subjects were azoospermic and 32% severely oligozoospermic. Six months after release of suspension the semen quality was normalized.

It is noteworthy that the sperm count reduction after testicular suspension was more manifest in stitch than in ball suspension, although the difference was insignificant. Accordingly, the increase in the sperm count after suspension release occurred earlier in ball than in stitch suspension. The difference in results between the 2 suspension procedures, albeit insignificant, could be related to the invariably firm position of the stitch-suspended testicle which unlike the unfixed ball-suspended testicle remains unaffected by the subject's movements in his daily activities.

Testicular suspension was accompanied with a significant decrease in serum testosterone and an increase in serum prolactin. These hormone levels were normalized after suspension release. The testicular biopsy showed tubular degenerative changes during suspension, which recovered after release.

The above mentioned results point to a deleterious effect of testicular suspension on the testicular function and its restoration after suspension release. The role of these testicular changes in contraception was tested. Pregnancy did not occur during the suspension period. During the first 3 post-suspension months, sexual intercourse was not practiced because the changes in the testicular function were not adequate yet to guard against pregnancy. After release of testicular suspension, one third of the wives conceived in the first 6 months post-release, and the remaining two thirds in the following 8 months.

It is worth mentioning that fetal anomalies were not encountered during pregnancy or after delivery. Furthermore, there were no abortions during the study period.

3 Polyester-induced azoospermia

3.1 Technique

Another issue we investigated recently is the vulnerability of spermatogenesis to polyester (polyethylene terphthalate) contained in textile products^[26-28]. An earlier study^[26] showed that dogs when made to wear polyester underpants had a diminished sperm count which was reversible when the pants were removed. In contrast, dogs wearing cotton pants showed insignificant semen changes. A human study revealed that polyester underpants worn by men generated an electrostatic field that traversed the scrotum and seemed to affect the testicle and/or the epididymis, leading to diminished spermatogenesis. Textiles worn by 33 volunteers in 3 equal groups during 18 months produced insignificant changes in testicular temperature and serum reproductive hormones^[27]. In the first group of 11 subjects who wore polyester underpants, 4 showed a significantly decreased sperm count and testicular degenerative changes by the 14th month; these changes were reversed after the underpants had been removed. In the second polyester-cotton mix group of 11 subjects, only 1 volunteer became oligospermic 16 months into the pants-wearing period; the sperm count was normalized after removal of the underpants. In the third group of 11 wearing cotton only, insignificant changes in the semen character appeared.

The results of these studies led to conclude that polyester fabrics have a depressive effect on the spermatogenesis^[27] and that this effect was reversible on removal of the pants. It further appeared that this effect is related to the electrostatic charges generated by the polyester fabrics and creating an electrostatic field across the testicle and/or the epididymis.

It was therefore surmised to use polyester-containing textiles as a contraceptive tool for men^[28]. The contraceptive effect of a polyester sling applied to the scrotum was studied in 14 men who wore a polyester suspensor  for 12 months.

The suspensory sling consisted of polyester fabric and was fashioned for the scrotum to lie within it (Figure 1). Variable sizes of the sling were made to suit the scrotum and slung to the waist of the subject by a belt attached to the suspensor. The belt was tied so that the suspensor elevated the testicles towards the abdomen. The suspensor was used day and night and was changed when soiled. Follow-up investigations comprised periodic check of semen character, testicular size, rectal-testicular temperature difference, serum reproductive hormones, and testicular biopsy. The electrostatic potentials generated by friction between the polyester suspensor and the scrotal skin were determined. Female partners used contraceptives until the men became azoospermic. After 12 months, the suspensor was abandoned and the aforementioned investigations were performed again^[28].

Figure 1. Scrotal sling (from Shafik^[28]).

3.2 Results

In the suspensor-wearing period, all men became azoospermic after (139.620.8) days (data expressed in the means), with decreases in both testicular volume (P<0.05) and rectal-testicular temperature difference (P<0.001). Serum reproductive hormones showed no significant change (P>0.05).  Seminiferous tubules revealed degenerative changes. No pregnancy occurred during this period. The polyester suspensor generated electric potentials (366.430.5) V/cm² by day and (158.313.6) V/cm² by night^[28].

In the period after the suspensor was abandoned, the sperm concentration returned to the pre-test level in a mean period of (156.614.8) days. Likewise, the testicular volume and rectal-testicular temperature difference were normalized.  In 5 couples the women conceived as they had planned.

3.3 Comments

Our study^[28] demonstrates that the ensheathing of the scrotum in a polyester suspensor has induced azoospermia in all of the 14 volunteers and that this azoospermia is reversible following the release of the suspensor, and the wives of 5 of the volunteers became pregnant according to plan.

Furthermore, the study shows that electrostatic potentials are generated from the polyester sling and the opposing scrotal skin as a result of friction between the two surfaces. They are higher during daytime rather than at night, due probably to the higher temperatures prevailing during the day. The electrostatic charges and consequently the potentials are directly proportional to the temperature: the higher the temperature, the more charges are generated.

3.4 Azoospermic effect of the polyester sling

The azoospermic effect of the polyester sling seems to be related to two factors^[26-28]: the electrostatic field effect and the disordered thermoregulatory effect.

3.4.1 The electrostatic field effect

Friction between the scrotal skin and the polyester sling creates a negative charge on the inner surface of the sling and a positive one on the scrotal skin facing the sling (Figure 2). An equal but opposite charge to the one on the inner sling aspect occurs on the outer sling surface. The result is that the outer surface of the scrotal sac facing the sling will have a number of positive charges. The latter produces induced charges with negative sign on the other surface of the scrotal sac. Eventually, equal but opposite charges are created on the two aspects of the scrotal sac: the one in contact with the sling and the other away from it (Figure 2). These opposite charges will produce an electrostatic field extending from one aspect of the scrotum toward the other through the scrotal sac^[26-28]. The electrostatic field traversing the scrotal contents would disturb the testicles and/or epididymis leading to diminished spermatogenesis.

Figure 2. Diagrammatic illustration of the electrostatic potentials created on the polyester suspensor and the scrotal sac. The electrostatic field is demonstrated (from Shafik^[26]).

3.4.2 Disordered thermoregulation

The polyester suspensor leads to spermatogenic depression also by disturbing the testicular thermoregulatory mechanism. The suspensor induces disturbed thermoregulation by two mechanisms. Firstly, it fixes the two testicles to the effect that they cannot move in reaction to changes in the environmental temperature^[13,14]. Secondly, it slings the two testicles up towards the warm abdomen, thus increasing the testicular temperature with a resulting decrease in the rectal-testicular temperature difference. The testicular temperature may as well affect the frequency of the electrostatic potentials generated on the scrotal skin. As mentioned earlier, the higher the temperature, the more charges are generated. Thus, with the temperature of the testicles increasing as a result of their being close to the warm abdomen, the generated electrostatic charges increase, and their possible injurious effect on the intrascrotal structures would consequently be increased. In all volunteers a decrease in the rectal-testicular temperature difference during the period when the polyester suspensor was worn, was recorded. However, the temperature difference returned to the pre-test value after the suspensor was released.

3.5 Polyester sling as a contraceptive tool 

4 Prolactin Injection

In our contribution to the search for a safe, effective, convenient and reversible contraceptive method, we have taken advantage of the properties of prolactin (PRL) to try its use as a male contraceptive method^[29].

PRL is a protein hormone secreted by the anterior pituitary gland. Its secretion seems to be inhibited by a PRL release-inhibiting hormone which may be dopamine^[30,31]. Hyperprolactinemia has been found in infertile patients with oligo- or azoospermia^[32,33]. Furthermore, lactational hyperprolactinemia seems to be decisive for maintaining lactational amenorrhea which is known to have a contraceptive effect.

4.1 Technique

The method was tested in dogs: 14 test and 14 control^[29]. The dogs in the test group were injected with ovine PRL in a dose of 600 g/kg of body weight weekly for 6 months. During this period, the testicles, semen, reproductive hormones, renal function, and serum sodium and potassium were examined periodically. Testicular biopsy was obtained 3 and 6 months from PRL administration. These investigations were repeated during the 6 months following withdrawal of the drug.  

4.2 Results

The sperm count dropped gradually with a decrease in sperm motility and an increase in abnormal forms, and azoospermia was reached within 3 months after PRL administration. Testicular biopsy showed degenerated seminiferous tubules. Reproductive hormones, renal function as well as serum sodium and potassium revealed insignificant change (P>0.05). Dog mating during the period of PRL administration produced no pregnancy. Three months after drug withdrawal, the sperm count was normalized and mating produced pregnancy; the offspring showed no anomalies.

4.3 Comments

Our study demonstrates that PRL inhibits spermatogenesis^[29]. The sperm inhibition started about 2 weeks after PRL administration, approached azoospermia in 6 weeks and reached azoospermia in all the dogs within 3 months.  The diminished sperm density was accompanied by decreased motility and increased abnormal forms of sperm.  These changes in the spermiogram were accompanied with degenerative changes in seminiferous tubules and continued to the end of the 6-month period of PRL administration.  Meanwhile, no significant changes were encountered in renal function or in the serum levels of sodium and potassium.  Glycosuria was not detected which would indicate that the carbohydrate metabolism had not been affected. The reproductive hormones showed insignificant changes at 3 and 6 months after PRL administration. It does not exclude the possibility that gonadotropin and testosterone secretion may be suppressed if they have been assessed at an early date of PRL injection. After 3 months of PRL administration, pregnancy did not occur despite repeated inseminations.

Three months after drug withdrawal, 85.7% of the dogs had a normal spermiogram. Five months from withdrawal, all dogs had a normal semen character and produced pregnancy with healthy offsprings in all of the 9 inseminated bitches. These results demonstrate the effectiveness of PRL in inducing reversible spermatogenic depression without lasting changes in serum reproductive hormones or renal function.  Potency and libido would thus not be affected because serum testosterone levels are not affected.

It has been reported that PRL and growth hormones can produce renal retention of water, sodium and potassium that persists for 12 to 18 hours after PRL administration^[34,35]. In our study, no significant changes could be detected in these parameters^[29]. This could be due to the fact that the injections were spaced weekly.

The cause of the anti-spermatogenic action of PRL is so far unknown. Reproductive hormones were not measured frequently enough to determine the effect of any suppression of gonadotropin secretion.  In addition, the spermatogenic depression could be due to a direct action of PRL on the testicle.  The degenerated seminiferous tubules may provide indirect evidence for this possibility; a direct relationship between the two events, PRL administration and testicular injury, could however not be verified in our study but is a point that calls for further investigation.

The results of the present study demonstrate that PRL has the potential to be developed as a male contraceptive, which is reversible.  The method is simple and has no complication.  The only disadvantage to date is that the drug is administrated by injection.  Nonetheless it seems to have the potential for paving the way to a prolactin pill as an efficient contraceptive method for males.

5 Acknowledgment

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