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Nirmal K. Lohiya, B. Manivannan, Pradyumna K. Mishra, Neelam
Pathak
Asian J Androl 2001 Jun; 3: 87-95
3 Vas deferens as a target organ
Although the transport of spermatozoa from the testis towards the ejaculatory duct could be altered or arrested at the level of the testis, epididymis or vas deferens, the vas deferens is the site where intervention would be possible with minimal hormonal and systemic interference and may give better scope for reversal. The present review summarizes the advantages and disadvantages of the issues related to various vas-based methods of contraception.3.1 Vasectomy
Vasectomy is the first vas-based surgical male contraceptive
method and the only effective technique known as the most simple, popular
and readily available form of voluntary family planning for men. It provides some major
advantages that no other
birth control measure can offer. It is safe, with minimal morbidity and almost
no mortality, effective and simple as a one step procedure. It requires minimal training for most
surgeons, taking only 10-15 minutes on an out-patient basis and is inexpensive compared with female
sterilization which requires more extensive surgery and equipment. In the past
three decades, it has been practiced in over 40 million couples world
wide[9].
However, in India, only 2% of reproductive age males rely on
vasectomy for birth control, mainly because it is a surgical
intervention and of the false apprehensions that the procedure reduces sexual
potency[6]. Contraindications to vasectomy include scrotal pathology,
haematoma, allergy to local anaesthesia, genito-urinary or groin infections and
sperm granulomas[10,11]. Fear of cardiovascular sequelae and an
increased risk of prostate and testicular cancer have also been
indicated[6]. A WHO consultation reviewed the available evidences and
reported that ¡°any casual relationship between vasectomy and the risk of cancer
of the prostate or testis is unlikely and that in the existing family planning
polices of WHO towards vasectomy, no changes are warranted¡±[12]. In
India, studies carried out
by the Indian Council of Medical Research and others have shown that vasectomy
has no adverse effects on the cardio-vascular system and does not cause prostate
cancer[13-16]. In Denmark, over 73,917 vasectomized men were
identified and registered between 1977 and 1989 without indication of increased
risk of testicular cancer due to vasectomy[17]. While these
conclusions are
encouraging, it will be important to continue monitoring the safety of
vasectomy.
3.1.1 No-scalpel vasectomy
A refined technique for vasectomy that eliminates the use of a
scalpel, has been developed and widely practiced
since its inception. It
is less invasive, being performed under local
anaesthesia using
specially designed vas fixing forceps that encircle and firmly fix the vas
without penetrating the skin. A curved sharp pointed haemostat is used to puncture the skin
and vas sheath, and to
expose the vas which is then occluded as in conventional
vasectomy[19,20].
The procedure offers many advantages compared to conventional
vasectomy, e.g. no incision, no stitches, faster procedure, faster recovery,
less chance of bleeding and other complications, less discomfort and high
efficiency, which have helped the technique to increase the acceptability of
male sterilization in many parts of the world[21]. In India, the
technique was acceptable to more educated and higher income men and the number
of vasectomy acceptances increased three times as compared to the conventional
counterpart during the corresponding period[22,23]. However, similar
to conventional vasectomy, this method also does not assure a successful
reversal.
3.2 Biomedical devices
An ideal intravasal device used for male contraception should be easy to insert, flexible, prevent sperm passage and be capable of easy removal to restore vas patency and so permit the return of fertility[24]. Initial attempts have been made to solve the problems associated with the reversal of vasectomy. Several biomedical devices have been developed with the aim of having safe and reversible vas occlusion in animal models and in man.3.2.1 Intravasal thread (IVT)
It has been shown that the passage of spermatozoa could be
blocked by placing surgical nylon or silk thread intravasally. Sperm passage was
inhibited temporarily and the luminal patency of the vas could be restored by
removing the intravasal thread (IVT)[25]. However, in the course of
time, a small portion of the vas lumen underwent dilation due to the
increased intravasal pressure caused by the accumulation of spermatozoa which allows
spermatozoa to pass through the dilated
lumen[26]. To
avoid such problems, an intravasal thread, made of non-reactive and
non-absorbable surgical thread with two strings of black filiform nylon was
placed in the vas lumen.
As long as the IVT remained in place in the vas, sperm passage was successfully
inhibited. When the IVT was removed , the patency of the vas lumen was restored. The filiform nylon
attached to the proximal end of the IVT was tied around the vas and held the IVT in place,
preventing sperm from
escaping through the dilated vas lumen and permitting easy and satisfactory
restoration of patency by removal of the IVT. Histological studies showed no
tissue reaction in the vas. The prevention of sperm passage is believed to be
due to mechanical obstruction by the IVT[27,28]. This study laid a
foundation for a variety of other occlusive techniques that followed.
3.2.2 Intravasal copper wire
In vas occlusion methods, spermatozoa are accumulated in the
epididymis and initiate some immunological reactions, leading to a rise in serum
antisperm antibody titres.
Although, not fully confirmed, the available data suggest that the high antisperm antibody titre contributes to the low pregnancy success
rate despite effective vasovasostomy procedures.
Hence, in order to avoid the occlusive intravasal thread
procedure, a slightly modified, non-occlusive copper
wire has been used[33]. When the spermatozoa come in contact with
copper there are toxic alterations in the acrosomal enzymes (particularly in
those containing sulphydryl groups) leading to a loss in functional capacity. Copper may also
displace zinc from the
acrosome[34,35]. In animals intravasal copper wire leads to
decapitation of the spermatozoa and infertility. If one end of the copper wire
was left protruding outside the vas wall, reversal was possible by removal of
the wire and the return
of fertility rate was
significant. The major shortcomings of this procedure are that sperm granuloma
often occurs at the site
where the wire emerged from the vas wall and that the effectiveness of the
procedure declines with
time due to erosion of the copper wire[33].
3.2.3
Intravasal electric device
Another approach uses the principal that
electrical current induces morphological changes in the sperm acrosomal
membrane. To deliver an electric current, an external battery or a miniature
battery inside the body has been tried [36]. In the external battery
system, the leads
entering the body posed risk of recurrent infection. The miniature
battery, on the other hand, was impractical as the energy storage was very
small. The battery becomes drained in a short time necessitating frequent
surgical manipulations.
As an alternative approach, a biogalvanic cell has been used.
When the electrolytes in the fluid in the vas comes in contact with two
dissimilar metals/materials well apart in the electrochemical series, an
electric current is generated which will kill the spermatozoa. The biogalvanic
cell may be the choice for affecting the viability and fertilizing ability of
spermatozoa inside the vas lumen[33]. Based on this principle, Misro
et al[37] developed non-occlusive male contraceptive devices
using different combinations of materials, such as, copper, silver,
copper-aluminium, silver-aluminium, silver-graphite and graphite-aluminium. The
graphite-aluminium combination was found to be the most effective. The
electrodes were placed in a teflon housing with short inlet and outlet tubes
which were connected to
the proximal and distal ends of the vas deferens. This device in rats produced
infertility, when the shorting link was closed, leading to current flow.
Fertility was restored upon disconnecting the shorting link. The device can be
designed in such a way that the closing and opening of the shorting link can be
done through the intact scrotal skin by palpation[33]. However,
hitherto no further research
on this procedure
has been reported.
3.2.4 Bionyx control valve (phaser)
This is another implantable, reversible
intravasal device, developed by Bionyx
Guha et al[39] described an intravasal
device in rhesus monkeys comprised of two stainless steel tubes of outer
diameter 0.6 mm linked by means of a biocompatible teflon body and a plunger
with a cylindrical channel. When the plunger is pushed down, the communication
between the tubes is blocked and azoospermia is obtained. When the plunger is
pulled up, spermatozoa will pass through. The device is implanted bilaterally
between the cut ends of the vas deferens through a high scrotal incision.
Manipulations of the plunger is possible either by palpation on the scrotal skin
or through a small scrotal incision. Contraceptive efficacy over a period of six
months was
demonstrated[33].
3.2.5 Tantalum clips
An extravasal procedure, that involves placement of
compression clips over the scrotal skin and pressing over the vas deferens, has
also been investigated. Tantalum clips on the vas deferens of dogs produced
azoospermia for a short period but leakage of spermatozoa ensued
thereafter[40]. In rabbits azoospermia was reported for a 15 month
study period[41]. However, the hope of easy removal of the clips for
restoration of fertility was not supported by actual experience. Fibrous
epithelium which formed surrounding the clip made removal
difficult[33].
3.3 Percutaneous injection
With the Biomedical devices approaches, implantation of the
devices required highly specialized microsurgery which cannot be carried out on
an out-patient basis and
over an extended period of time. Besides, an unacceptably high incidence of displacement of the devices out
of the vas deferens was noted.
A radically different concept based on inhibiting sperm
transport by injecting chemical agents into the lumen
of the vas deferens has been developed which minimised the surgical intervention
in the scrotal region. It is a further improvement on the no-scalpel technique
and is claimed to be completely non-surgical[42,43]. In this method
the vas deferens is secured firmly by a specially designed vas clamp, a puncture needle is
accurately inserted into the vas and then replaced by an injection needle; then
the fertility limiting substance, such as sclerotic or non-sclerotic chemical
agents, is injected[44]. One major disadvantage, however, with this
method is that it is a delicate procedure and requires training and precision.
However, once the technique is mastered, this method generally takes only ten
minutes[42,43].
3.3.1 Chemosterilization
After the advent of the percutaneous injection method, at least 26 different
combinations of chemicals have been tried to achieve permanent
sterilization[43,45,46]. The major requirements of the intravasal
chemicals are that, they must be non-toxic and sufficiently sclerotic to produce
enough scarring on the vas wall to block it.
Initially a combination of carbolic and n-butyl alpha
cyanoacrylate has been tried in over 600,000 men. The compound is a sclerotic
agent which solidifies
within 20 seconds after injection into the vas lumen and produces a complete
blockage of the vas deferens by adhering permanently onto the luminal surface of
the vas[47]. Over 96 per cent of cases have been reported to be
azoospermic[46,48] and 90 per cent effectiveness over
900 men for 9-12 months has been reported in a WHO based study[49].
Li and Zhu[50] reported an azoospermic rate of 96% with 99% pregnancy prevention in their
eight year follow up study after injection. Studies on pharmacological,
toxicological and clinical effects have shown that this compound has no toxic or
carcinogenic effects in experimental animals. Ten-year follow up of 822 cases
found no long-term complications. In a further study of 3073 cases, 62 children
were born to 60 couples
with normal development and intelligence, thus ruling out the possibility of
teratogenicity[47]. The method has cleared WHO toxicological
tests[49]. However, this method gives permanent sterilization
and does not offer chances of reversibility[46,48].
Freeman and Coffey[51] tested a series of sclerotic
agents viz., 95% ethanol, 10% silver nitrate, 36% acetic acid, 3.6%
formaldehyde, 3% sodium tetradecyl sulphate, 5% sodium morrhuate , 5% potassium
permanganate and 3.6% formaldehyde in 90% ethanol in the vas deferens of rats
and dogs. Five per cent sodium morrhuate and potassium permanganate were shown
to be ineffective in producing complete sterility while the other agents
resulted in complete sterility eight months following a single injection. The
lumen of the vas deferens was damaged and replaced by scar tissue and was free
of spermatozoa. The technique is simple and requires no surgery and it has been
claimed that once it has been learnt, it can be done quickly and with less expense.
Following the success of the technique in rats and dogs, Coffey and
Freeman[52] produced sterility in a small number of human volunteers
with a percutaneous injection of 90% ethanol containing 3.6% formaldehyde into
the vas deferens. Although this procedure appears promising, the sterilization
is permanent and there is no evidence of vas recanalization and return of fertility. Dixit et
al[53] described that this procedure leads to testicular atrophy
and impairment of Leydig cell function. Gallegos et al[54]
however, reported that a potent phlogogenic agent, carrageenan, did not produce
any effect in the treated animals. They also reported that asingle injection of
a mixture of sclerotic agents, containing quinacrine hydrochloride, chloroform,
magnesium stearate and carbopol, resulted in azoospermia after 4 weeks of treatment in
rabbits. A spontaneous reversal of quinacrine vas occlusion following 6 months
has also been reported in rhesus monkeys[55]. The common tissue
adhesive, methyl cyanoacrylate has also been shown to produce complete vas
occlusion in 60 days in rhesus monkeys[56]. In another approach, a
single intravasal administration of 50 ¦ÌL neem oil, injected bilaterally,
induced sterility in rats. The treatment resulted in a block of spermatogenesis
without affecting testosterone production; the seminiferous tubules, although
reduced in diameter,
appeared to be normal and contained early spermatogenic cells. The
histology of the epididymis and vas deferens was normal without any inflammatory
reaction or obstruction. No anti-sperm antibodies could be detected in the
serum. Unilateral administration of neem oil in the vas resulted in a
significant reduction of testicular size and spermatogenic block which only
occurred on the side of application. The draining lymph node cells of the
treated side showed an enhanced proliferative response to in vitro mutagen
challenge. It was suggested that the testicular effects following intra vasal
injection of neem oil may
possibly be mediated by a
local immune mechanism[57]. With a similar approach to block spermatogenesis an intravasal
injection of Bacillus Calmette Guerin (BCG), which is shown to provide immune
competent cell access to seminiferous tubules, thereby elicited an autoimmune reaction against
haploid-spermatogenic cells[58,59], but it failed to produce
infertility in rats[60]. Male fertility regulation by intravasal injection of
controlled-releasing gossypol has also been reported[61].
3.3.2 Injectable plugs
Zhao[62] employed percutaneous injection of polyurethane elastomer
to form plugs. These plugs are designed for
easy removal and are ideal for men who would like the possibility of
reversal in the case of
unforeseen circumstances. In China before 1990, over 12,000 men have been
using the elastomer. Over 98% cases showed pregnancy protection for
at least 5 years after insertion[63]. Azoospermia was found in 38%,
85% and 96% of men, 6, 12 and 24 months after injection of the elastomer,
respectively[63,64]. Studies on over 130 men indicated that
these plugs could be
easily removed up to 5 years after insertion and were associated with pregnancy in the spouses of
all men studied[44,62,63]. However, as it is a total vas occlusion,
the body system is likely to develop anti-sperm antibodies, leading to
irreversibility even after plug removal. Such a critical analysis has not been
made available[65]. Another shortcoming is that the plug may lead to
rupture of the vas[64]. Toxicological uncertainties about the
presence of aromatic amines in polyurethane plugs have also been raised, but
follow up of acceptors of the method has not so far revealed any justification
for this concern[63].
As an alternative, intravasal injection of formed-in-place
silicone rubber for vas
occlusion has been tried in a small number of human
volunteers[66,67]. Azoospermia was obtained after 5 months in 3 men
and by 9 months in all men[66]. A comparative study revealed
that the azoospermia rate
achieved in 3ª²6 months was comparable to that of no-scalpel
vasectomy[24,67]. It is claimed that silicone rubber does not
interfere significantly in vas physiology and once the plug is removed, the
mucosa cells of the vas will soon regenerate to allow free flow of
spermatozoa[24,67]. However, details regarding the reversibility
trial of silicone rubber vas occlusion are thus far not available.
3.4 Non-injectable plugs
Silicone plugs, called ¡®the Shug¡¯ is a non-injectable plug
alternative[68]. The main advantage of this method over injectable
plugs is its double design. It is composed of two silicone plugs with nylon
tails to help anchor the plugs to the vas, thus giving it the potential to be
more leak free, i.e., any spermatozoa which leak past the first plug are likely
to be trapped in the space between the plugs. Double plugs could be more
reliable than the single one[20].
The Shug can be inserted into the vas by the ¡®no-scalpel
method¡¯. Removal of the plug requires minor surgery.
Full return of fertility after seven months of Shug use has been reported in
monkeys[69]. However, this is not a sufficient time for
the development of anti-sperm antibodies, which may affect the complete return of fertility. Thus
studies on safe reversal with complete return of fertility have not yet been done.
Clinical trials revealed 97% decrease in motile sperm counts in the men
studied[70]. The Shug has several advantages: the size of the preformed plug in
relation to the size of the vas deferens could be controlled, thus avoiding the
possible rupture of the vas; the anchoring mechanism can prevent the migration of
the plug along the length of the vas. The preformed plug also avoided the
possibility of entry of toxic substances during the hardening processes as in
the case of injectable silicone rubber[68]. In primates, removal of
the Shug resulted in the
normal passage of the spermatozoa[69]. Studies involving modifications of Shug devices
and insertion techniques are ongoing.
3.5 Styrene maleic anhydride (SMA)
Styrene maleic anhydride is a co-polymer of maleic anhydride
and styrene. In
preliminary studies on rats, rabbits and monkeys[71-75], it
was shown that when the compound styrene maleic anhydride (SMA) comes in contact
with body fluids, the acid
maleic anhydride is hydrolysed and the carboxyl group exerts a pH lowering effect, which is limited
to the immediate vicinity
of the polymer. The body fluid is a buffer solution and an equilibrium state
between the hydrated and swollen polyelectrolyte SMA and its environment is
established like a Donnan membrane equilibrium[76].
The efficacy of SMA as an intravas contraceptive has been
tested in albino rats[71,72,77] and in rabbits and
monkeys[73,74,78,79]. The procedure offers long term fertility
control through several
factors: 1) it blocks the passive transport of sperm; 2) it has a pH
lowering action that is deleterious to spermatozoa; and 3) the polymer generates
a positive charge that disturbs the negative charge of the sperm head membrane,
ultimately resulting in rupture of the acrosomal membrane leading to loss of
fertilizing ability[76,80].
In
experiments in langur monkeys, an animal model close to humans in
reproductive anatomy and physiology[81-83], SMA, 60 mg in 120 ¦ÌL
DMSO injected as an intravasal occlusive
agent, led to severe
oligo/astheno/necro/teratozoospermia in the initial three ejaculates and to
uniform azoospermia subsequently. Studies of the ejaculated spermatozoa by scanning and
transmission electron microscopy revealed severe damage predominantly to the acrosome envelope and
mid-piece configuration, indicating the possibility of instant sterility after
vas occlusion with SMA[84]. The seminal plasma biochemistry and
toxicological parameters were unaltered in the vas occluded langur
monkeys[85]
indicating safety
of the drug in the animal.
The feasibility of intravasal administration of SMA and
its safety were tested in a Phase I clinical trial. Thirty
eight male volunteers were injected varying doses of SMA in the
range 5-140 mg into each
vas deferens; azoospermia was achieved with the higher doses of SMA. The
volunteers did not
experience any problem with their urinogenital system and
libido[80,86].
A phase II clinical trial has been conducted to
ascertain if a single injection of SMA into each vas impaired
fertility for at least
one year and to examine if
libido was affected. A
standardized dose regimen of 60 mg SMA per vas was administered to 12 volunteers by the conventional procedure,
and in another 4 volunteers, no-scalpel
injection of SMA was
performed. In all subjects, the treatment led to azoospermia and gave
pregnancy protection for the one year study period. The volunteers and their
spouses retained good health throughout the study[87]. A two year
exploratory trial in 20
volunteers with SMA ranging 40-70 mg injected into each vas
suggested pregnancy protection both in the azoospermic and non-azoospermic
status with transient minimal side effects and no effect on
libido[88].
4 Conclusion
Among the options available for the regulation of male fertility, disruption of sperm transport in the vas deferens is an attractive one. Vasectomy, either by conventional or no-scalpel method is in use world wide as a simple and effective approach despite its several limitations. Intravasal occlusion with plug, Shug or medical grade silicone rubber (MSR), although claimed to induce reversible azoospermia without interrupting spermatogenesis, requires skilled microsurgery for the implantation and removal of these compounds. The non-sclerotic occlusive polymer SMA is proposed to be more advantageous than vasectomy and other occlusive agents in that it could be a totally non-invasive procedure with no-scalpel injection and a non-invasive reversal method. These procedures offer several modes of fertility control mechanisms, providing instant infertility as well as long-term contraceptive efficacy without significant adverse effects. There is also the possibility of using this method for male spacing by repeated vas occlusion followed by non-invasive reversal. The drug has been named RISUGR and is currently undergoing multicentre Phase III clinical trial. It is concluded that this option is likely to meet the need for long-term reversible male contraception with minimal invasive intervention in the near future.Acknowledgements
Investigations on Styrene Maleic Anhydride (SMA) are supported by the Ministry of Health and Family Welfare, Government of India, New Delhi.References
[1] Handelsman DJ. Hormonal male contraception. Int J Androl
2000; 23 (suppl 2): 8-12.
[2] Huhtaniemi I. Current challenges of andrology.
Asian J Androl 1999; 1: 3-5.
[3] Waites GMH. The contribution of asian
scientists to global research in andrology. Asian J Androl 1999; 1: 7-12.
[4]
Sriraman V, Rao AJ. Current status in development of male contraceptives.
In: Chowdhury SR, Gupta
CM, Kamboj VP, editors. Current status in fertility regulation: indigenous and
modern approaches. Lucknow: CDRI; 2001. p 163-78.
[5] Rajalakshmi M,
Sharma RS. Methods for the
regulation of male fertility. In: Chowdhury SR, Gupta CM, Kamboj VP,
editors. Current status in fertility regulation: indigenous and modern
approaches. Lucknow: CDRI; 2001.
p 179-209.
[6] Puri CP, Gopalkrishnan K, Iyer KS. Constraints in the
development of contraceptives for men. Asian J Androl 2000; 3: 179-90.
[7]
Hair WM, Wu FCW. Male contraception: prospects for the new millennium. Asian J
Androl 2000; 2: 3-12.
[8] Wang CCL. Clinical studies using androgens alone
for male contraceptive development. In: Rajalakshmi M, Griffin PD, editors. Male
contraception: present and future. New Delhi: New Age Int (P) Ltd; 1999. p 189-200.
[9] Liskin L,
Benoit E, Blackburn R. Vasectomy: new opportunities. Baltimore, Population
Information Programme, John Hopkins University; 1992.
[10] Lipshultz LI,
Banson GS. Vasectomy: an
anatomical, physiological and surgical review. In: Cunningham GR, Schill
GR, Hafez ESE, editors. Regulation of male fertility. Hague: Martinus Nijhoff ; 1980. p 159-86.
[11] Silber SJ.
Vasectomy. In: Knobil E, Neill JD, editors. Encyclopedia of reproduction.
California: Academic Press; 1998. p 977-85.
[12] Waites GMH.
Male contraception: recent developments. WHO Report Series;1998. p 1-8.
[13] Indian Council
of Medical Research, Task Force on Male Fertility Regulation. Long-term effects of vasectomy.
Part I: Biochemical parameters. Contraception 1983; 28: 423-8.
[14] Tripathy
SP, Ramachandran CR, Ramachandaran P. Health consequences of vasectomy in India.
Bulletin WHO 1994; 72: 779-81.
[15] Platz EA, Yeole BB, Cho E, Jussawalla DJ,
Giovannucci E, Ascherio A. Vasectomy and prostate cancer: a case
control study in India. Int J Epidemiol 1997; 26: 933-7.
[16] Soonawalla FP.
Vasectomy-safety and reversibility. In: Rajalakshmi M, Griffin PD, editors. Male
contraception: present and future. New Delhi: New age Int(P) Ltd; 1999. p 251-63.
[17] Moller H,
Knudsen LB, Lynge E. Risk of testicular cancer after vasectomy: cohort study of
over 73000 men. Br Med J 1994; 309: 295-8.
[18] Handelsman DJ. Hormonal male
contraception. In: Puri CP, Van Look PFA, editors. Current concepts in fertility
regulation and reproduction. New Delhi: Wiley Eastern Ltd; 1994. p
133-56.
[19] Li SQ, Goldstein M, Zhu J. The no-scalpel vasectomy. J Urol
1991; 145: 341-4.
[20] Hargreave TB. Towards reversible vasectomy. Int J
Androl 1992; 15: 455-9.
[21] Xu B, Huang WD. No-scalpel vasectomy outside
China. Asian J Androl 2000; 2: 21-4.
[22] Das HC,
Bhattacharjee J. No-scalpel vasectomy: hope for the future. J Fam Welfare 1993;
39: 14-6.
[23] Nigam SK, Malik SK, Das HC. A profile of acceptors of
non-scalpel vasectomy. J Fam Welfare 1994; 40: 19-21.
[24] Soebadi DM.
Medical grade silicone rubber vas occlusion: an alternative method of male
contraception. In: Rajalakshmi M, Griffin PD, editors. Male contraception:
present and future. New Delhi: New Age Int (P) Ltd; 1999. p 273-91.
[25] Kar AB,
Kamboj VP. Spermatozoa disintigration in rats with an intra-vas deferens device. Indian J Exp
Biol 1964; 2: 240-4.
[26] Lee HY. Studies on vasectomy: I. Experimental
studies on nonoperative
blockages of vas deferens and permanent introduction of nonreactive
foreign body in a vas.
Korean New Med J 1964; 7:
599-608.
[27] Lee HY. Experimental studies on reversible vas occlusion
by intravasal thread. Fertil Steril 1969; 20: 735-44.
[28] Lee HY. Studies on
vasectomy . IX. Current status of reversible vas occlusion method. Korean J Urol
1972; 13: 17-25.
[29] Kothari MM, Pardanani DS. Temporary sterilization of
the male by intravasal contraceptive device. A preliminary communication. Indian
J Surg 1967; 29:
357-63.
[30] Hulka JF, Davis JE. Vasectomy and reversible vas occlusion.
Fertil Steril 1972; 23: 683-96.
[31] Moon
KH, Bunge RG. Temporary occlusion of the vas deferens. Invest Urol 1970; 8: 292-8.
[32]
Kim SK. Preliminary report on reversible vas occlusion. Proceedings of 1st
National Seminar on Voluntary Sterilization: Korean Association of Voluntary
Sterilization,
¡°Voluntary Sterilization¡±, 1975.
[33] Guha SK. Bioengineering in
reproductive medicine. Boston: CRC Press; 1990. p 145-50.
[34] Steven FS,
Criffin MM, Chantler EN. Inhibition of human and bovine sperm acrosin by
divalent metal ions. Possible role of zinc as a regulator of acrosin activity.
Int J Androl 1982; 5: 401.
[35] Patel KL, Pillai KBD, Shahni SM. Effect of intravasal
copper wire on the
fertility and reproductive organs in rats. Indian J Med Res 1983; 77:
465.
[36] Mahajan S, Guha SK, Misro MM. A theoretical and scanning electron microscope study on the
electrically mediated inactivation of spermatozoa. J Biol Phys 1982; 10:
113-24.
[37] Misro MM, Kaur H, Mahajan S, Guha SK. An intravasal
non-occlusive contraceptive device in rats. J
Reprod Fertil 1982; 65: 9-13.
[38] Lynn CM, Politano V. Early experience with
the bionyx control valve (Phaser). In: Sciarra J, Zatuchni GI, Spiedel J,
editors. Reversal of sterilization. Hargerstown: Harper & Row; 1977. p 91-6.
[39] Guha SK, Ahmed
AM, Kaur H. Feasibility study of the reversible occlusion device for the vas
deferens. Med Biol Eng 1976; 14: 15-8.
[40] Jhaver PS, Davis JE, Lee HY,
Hulka JF, Leight G. Reversibility of sterilization using occlusion clip. Fertil
Steril 1971; 22: 263-9.
[41] Lohiya NK, Tiwari SN. Vasectomy and vas
occlusion by tantalum clip: a comparative study. Iugoslav Physiol Pharmacol Acta
1987; 23: 1-13.
[42] Goldsmith A, Edelman DA, Zatuchni GI. Transcutaneous
male sterilization. In: Zatuchni GI, editor. Research
frontiers in fertility regulation. Hagerstown: Harper & Row; 1985.p
1-8.
[43] Goldsmith A, Edelman DA, Zatuchni GI. Transcutaneous procedures
for male sterilization. Adv Contracep 1985; 1: 355-61.
[44] Li SQ, Zhu J.
Non-incisional sterilization
with intravasal drug injection (10-year follow-up on control of blocking
the length of the vas deferens). Adv Contracep 1986; 2: 241.
[45] Davis JE.
Vasectomy. In: Lipshultz LI, Corriere JN, Hafez ESE, editors. Surgery of the
male reproductive tract. Hague: Martinus Hijhoff; 1980. p 143-56.
[46] Xiao
BL. Chemical vas occlusion in the People's Republic of China. In: Diczfalusy E, Bygdeman M,
editors. Fertility regulation today and tomorrow. New York, Serono Symposia Publication:
Raven Press; 1987. p 265-74.
[47] Nirapathpongporn A. Vas occlusion and
reversal. In: Boutaleb Y, Gzouli A, editors. Progress in contraception. New
Jersey: The Parthenon Publishing Group; 1991.p 3-12.
[48] Li SQ. Clinical
applications of the vas deferens puncture. Chinese Med J 1980; 3: 69-70.
[49]
Lissner EA. Frontiers in nonhormonal male contraception: a call for research.
Male contraception information project report series; 1994.
[50] Li SQ, Zhu
J. Non-operative sterility research with an intravasal injecting drug, clinical
report. Presented at The Expert Committee Meeting on Training for Voluntary Surgical
Contraception (VSC). Rio de Janeiro; 1984.
[51] Freeman C, Coffey DS.
Sterility in male animals induced by injection of chemical agents into the vas
deferens. Fertil Steril 1973; 24: 884-90.
[52] Coffey DS, Freeman C. Vas
injection: a new non-surgical procedure to induce sterility in human
males. In: Sciarra JJ, Markland C, Speidel JJ, editors. Control of male
fertility. Hagerstown: Harper & Row; 1975. p 147-60.
[53] Dixit VP,
Lohiya NK, Arya M, Agarwal M. The effects of chemical occlusion of vas deferens on the testicular
function of dog: a preliminary study. Acta Europ Fertilitat 1975;
6:349-53.
[54] Gallegos AJ, Potts F, Pedron N. Occlusion of vas deferens
after a single intraluminal injection of carrageenan and other chemical agents
in rabbits. Arch Androl 1994; 32: 59-62.
[55] Malaviya B, Chandra H. Chemical
occlusion of rhesus vas with quinacrine and its spontaneous reversal. Indian J
Exp Biol 1980; 18: 1296-7.
[56] Chandra H. Chemical occlusion of vas with MCA in
rhesus monkey. Contraception 1986; 33: 47-50.
[57] Upadhyay SN, Dhawan S,
Talwar, GP. Antifertility effects of neem (Azadirachta indica) oil in male rats
by single intra-vas administration: an alternate approach to vasectomy. J Androl
1993; 14: 275-81.
[58] Talwar GP, Naz RK, Das C, Das RP. A practicable
immunological approach to block spermatogenesis without loss of androgens. Proc
Natl Acad Sci USA 1979;
76: 5882-5.
[59] Talwar
GP, Mallick A, Ramakrishnan S, Das C, Gupta SK, Tandon A, Naz RK, Shastri N,
Manhar SK, Singh OM. Immunointerception of fertility. In: Wegmann TG, Gill TJ,
editors. Immunology of reproduction. New York: Oxford University Press; 1983. p
447-67.
[60] Singh SK, Rovan E, Frick J. Intravasal application of BCG
(Bacille Calmette Guerin)
is not an effective method for control of fertility in the male: a preliminary
report. Contraception 1993; 47: 303-6.
[61] Ye W, Lu G, Den Y. Effect on
intra-vas deferens injection of gossypol-polylactic acid on fertility and
spermatogenesis in rats. Chinese Med Sci J 1993; 8:20-4.
[62] Zhao SC.
Vas deferens occlusion by percutaneous injection of polyurethane elastomer
plugs: clinical experience and reversibility. Contraception 1990; 41:
453-9.
[63] Zhao SC, Lian YM, Yu RC, Zhang SP. Recovery of fertility after
removal of polyurethane plugs from the human vas deferens occluded for up to 5
years. Int J Androl 1992; 15: 465-7.
[64] Chen ZW, Gu YQ, Liang XW, Wu ZG,
Yin EJ, Li-Hong. Safety and efficacy of percutaneous injection of polyurethane
elastomer (MPU) plugs for vas occlusion in man. Int J Androl 1992; 15:
468-72.
[65] Wang C, Swerdloff RS, Waites GMH. Male contraception: 1993 and
beyond. In: Van Look PFA, Perez-Palacios G, editors. Contraceptive research and
development 1984-1994, The road from Mexico city to Cairo & beyond. Oxford:
WHO & Oxford University Press; 1994. p 121-34.
[66] Zhao SC, Zhang SP, Yu
RC. Intravasal injection
of formed-in-place silicone rubber as method of vas occlusion. Int J
Androl 1992; 15: 460-4.
[67] Soebadi DM, Gardjito W, Mensink HJA.
Intravasal injection of
formed-in-place medical grade silicone rubber for vas occlusion. Int J Androl
1995; 18,Suppl 1: 45-52.
[68] Zaneveld LJD, De
Castro MP, Faria G, Derrick F, Ferraro R. The soft, hollow plug (¡°Shug¡±): a
potentially reversible vas deferens occlusive device. In: Rajalakshmi M, Griffin
PD, editors. Male contraception: present and future. New Delhi: New Age Int (P)
Ltd; 1999. p
293-307.
[69] Zaneveld LJD, Depel W, Burns JW, Shapiro S, Beyler S.
Development of a potentially reversible vas deferens occlusion device and
evaluation in primates. Fertil Steril 1988; 49:527-33.
[70] Zaneveld LJD, De
Castro MP, Derrick F. Clinical evaluation of a reversible vas deferens blocking
device- the shug. In: Proceedings IIIrd International Symposium on
Contraception, Heidelberg, Germany; 1990.
[71] Misro MM, Guha SK, Singh HP,
Mahajan S, Ray AR, Vasudeven P. Injectable non-occlusive chemical
contraception in the male-I. Contraception 1979; 20: 467-73.
[72] Verma K,
Misro MM, Singh H, Mahajan S, Ray AR, Guha SK. Histology of the rat vas deferens after injection of
a non-occlusive chemical contraceptive. J Androl 1981; 63: 539-42.
[73] Sethi
N, Srivastava, RK, Singh RK. Histological changes in the vas deferens of rats after
injection of a new antifertility agent ¡°SMA¡± and its reversibility.
Contraception 1990; 41: 333-9.
[74] Sethi N, Srivastava, RK, Singh RK. Male
mediated teratogenic potential evaluation of new antifertility compound SMA in
rabbit (Oryctolagus cuniculus). Contraception 1990; 42: 215-23.
[75] Sethi N,
Srivastava, RK, Singh RK, Bhatia GS, Sinha N. Chronic toxicity of styrene maleic
anhydride, a male contraceptive, in rhesus monkeys (Macaca mulatta).
Contraception 1990; 42: 337-47.
[76] Guha SK. Contraceptive for use by a
male. USA Patent, 5488075; 1996.
[77] Sethi N, Srivastava, RK, Singh RK.
Safety evaluation of a male injectable antifertility agent, styrene maleic
anhydride, in rats. Contraception 1989; 39: 217-26.
[78] Guha SK, Ansari S,
Anand S, Farooq A, Misro MM, Sharma DN. Contraception in male monkeys by
intra-vas deferens injection of a pH lowering polymer. Contraception 1985; 32:
109-18.
[79] Lohiya NK, Manivannan B, Mishra PK, Pathak N. Nonª²invasive
reversible vas occlusion with styrene maleic anhydride: a possible alternative
to vasectomy. In: Puri CP, Van Look PFA, editors. Sexual and reproductive
health: recent advances, future directions. New Delhi:
New Age Int (P) Ltd; 2001. p 249-68.
[80] Guha SK, Singh G, Anand S, Ansari
S, Kumar S, Koul V. Phase I clinical trial of an injectable contraceptive
for the male. Contraception 1993; 48: 367-75.
[81] David GFX, Ramaswami LS.
Reproductive system of North Indian langur (Presbytis entellus entellus
Dufresne). J Morphol 1971; 135: 89-130.
[82] Lohiya NK, Sharma RS, Puri CP,
David GFX, Anand Kumar TC. Reproductive exocrine and endocrine profile of female
langur monkeys Presbytis entellus entellus. J Reprod Fertil 1988; 82:
485-92.
[83] Lohiya NK, Sharma RS, Manivannan B, Anand Kumar TC. Reproductive
exocrine and endocrine profiles and their seasonality in male langur monkeys
(Presbytis entellus entellus). J Med Primatol 1998; 27: 15-20.
[84] Lohiya
NK, Manivannan B, Mishra PK. Ultrastructural changes in the spermatozoa of langur monkeys
Presbytis entellus entellus after vas occlusion with styrene maleic anhydride.
Contraception 1998; 57: 125-32.
[85] Mishra PK. Contraceptive efficacy of
styrene maleic anhydride (SMA) in the lumen of the vas deferens and its reversal
in langur monkeys, Presbytis entellus entellus Dufresne. Ph.D. Thesis. Jaipur
(India), University of Rajasthan; 1999.
[86] Guha SK. Injectable
contraceptives for the male. Exp Opin Invest Drugs 1995; 4: 537-43.
[87] Guha
SK, Singh G, Ansari S, Kumar S, Srivastava A, Koul V, et al. Phase II
clinical trial of a vas deferens injectable contraceptive for the male.
Contraception 1997; 56: 245-50.
[88] Guha SK, Singh S, Srivastava A, Das HC,
Bhardwaj JC, Mathur V, et al . Two-year clinical efficacy trial with dose
variations of a vas deferens injectable contraceptive for the male.
Contraception 1998; 58: 165-74.
[89] Koul V, Srivastava A, Guha SK.
Reversibility with sodium bicarbonate of styrene maleic anhydride, an intravasal
injectable contraceptive, in male rats. Contraception 1994; 58: 227-31.
[90]
Guha SK. Non-invasive reversal of intraluminal vas deferens polymer
injection-induced azoospermia-technology. Asian J Androl 1999; 1: 131-4.
[91]
Lohiya NK, Manivannan B, Mishra PK, Pathak N, Balasubramanian SPA. Intravasal contraception with
styrene maleic anhydride and its noninvasive reversal in langur monkeys
(Presbytis entellus entellus). Contraception 1998; 58: 119-28.
[92]
Manivannan B, Mishra PK, Lohiya NK. Ultrastructural changes in the vas deferens of langur monkeys
Presbytis entellus entellus after vas occlusion with styrene maleic anhydride
and after its reversal. Contraception 1999; 59: 137-44.
[93]
Lohiya NK, Manivannan B, Mishra PK. Repeated vas occlusion and
non-invasive reversal with styrene maleic anhydride for male
contraception in langur monkeys. Int J Androl 2000; 23:
36-42.
Correspondence to: Prof. N. K. Lohiya,
FNASc, Reproductive Physiology Section, Department of Zoology, University of
Rajasthan, Jaipur-302 004, India.
Tel: +91-141-701
809 Fax: +91-141-701 809
E-mail: lohiyank@hotmail.com &
lohiyank@rediffmail.com
Received 2001-05-15
Accepted 2001-05-24