Reversible inhibition of sperm under guidance

Reversible inhibition of sperm under guidance (RISUG), formerly referred to as the synthetic polymer styrene maleic anhydride (SMA), is the development name of a male contraceptive developed at IIT Kharagpur in India by Dr. Sujoy K Guha. Phase III clinical trials are underway in India, slowed by insufficient volunteers. It has been patented in India, China, Bangladesh, and the United States. In the United States, there are efforts to get FDA approval under the name Vasalgel.

Mechanism of action

RISUG works by an injection into the vas deferens, the vessel through which the sperm moves before ejaculation. In a matter of minutes, the injection coats the walls of the vas with a clear gel made of 60 mg of the copolymer styrene/maleic anhydride (SMA) with 120 µl of the solvent dimethyl sulfoxide. The copolymer is made by irradiation of the two monomers with a dose of 0.2 to 0.24 megarad for every 40 g of copolymer and a dose rate of 30 to 40 rad/s. The source of irradiation is cobalt-60 gamma radiation.

The effect the chemical has on sperm is not completely understood. Originally it was thought that it lowered the pH of the environment enough to kill the sperm. More recent research claims that this is not enough to explain the effect.

One explanation is that the polymer is an anhydride, and hydrolizes in the presence of water in the spermatic fluid. Due to the breaking of a cyclic group, the polymer becomes a hydride and has a positive charge. This disturbs the negative charge of the sperm membrane on contact. (From U.S. Patent 5,488,075)

Some theorize that the polymer surface has a negative and positive electric charge mosaic. The differential charge from the gel ruptures the sperm's cell membrane as it passes through the vas, stopping the sperm before they can start their journey to the egg.

"Within an hour, the drugs produce an electrical charge that nullifies the electrical charge of the spermatozoa, preventing it from penetrating the ovum," Dr. Guha said.

Advantages

Some of the advantages, according to Dr. Guha, are:

• Effectiveness - There has been only one unplanned pregnancy among partners of the 250 men who have been injected RISUG — apparently due to an improperly administered injection. Out of the 250 men who have been injected RISUG, 15 men received the injection more than 10 years ago.
• Convenience - There is no interruption before the sexual act.
• Non-invasiveness - The process, once it is refined and approved, is expected to be operation-free. Men can leave the hospital immediately after an injection and resume their normal sex lives within a week.
• Duration of effect - According to Guha, a single 60 mg injection can be effective for at least 10 years.
• Reduced side effects - After testing RISUG on more than 250 volunteers, neither Guha nor other researchers in the field report side effects other than a slight scrotal swelling in some men immediately following the injection, which goes away after a few weeks, though there are also unconfirmed reports of kidney problems (see Controversy section below for further details).
• Reversibility - The contraceptive action appears to be reversible by flushing the vas deferens with another injection of dimethyl sulfoxide or sodium bicarbonate solution. (The sodium bicarbonate solution cannot be used as the solvent in the initial injection since it would neutralize the positive charge effect.) Although this reversal procedure has been tried only on primates, it has been repeatedly successful. Unlike in a vasectomy (see Blood-testis barrier), the vas deferens is not completely blocked, the body doesn't have to absorb the blocked sperm, and sperm antibodies are not produced in large numbers, making successful reversal more likely than with a vasovasostomy.

Controversy

The thoroughness of carcinogenicity, teratogenicity, and toxicity testing in clinical trials has been questioned. In October 2002, India's Ministry of Health aborted the clinical trials due to reports of albumin in urine and scrotal swelling in Phase III trial participants. The Indian Council for Medical Research noted that dimethyl sulfoxide used as a solvent for the injection is known to cause kidney damage. Although the ICMR has reviewed and approved the toxicology data three times, some United States researchers say that the studies were not done according to recent international standards.

RISUG was resubmitted for a new round of tests at a US lab, and was approved as non-mutagenic in July 2005. With this new stamp of approval, the path to continued Phase III trials in India became clear.

In March 2006, the ICMR announced that Phase III trials of RISUG could resume at 4 centers around India. The announcement of this progress led to renewed interest in RISUG. Unfortunately, little progress has been made since March. The research centers do not have enough of the RISUG compound to move forward with the trial. Marksans, the pharmaceutical company which has a manufacturing agreement with the inventor and the government, is now over a year past its initial April 2005 product delivery estimate. It is not clear why the delay continues.

Once this form of contraception is released into the market, it could displace the use of condoms. Unlike condoms, RISUG provides no protection against the spread of sexually transmitted diseases. A study, however, is underway to test the efficacy of RISUG as an anti-HIV agent, due to a hypothesis that the styrene maleic acid lowers pH to a level sufficient to destroy HIV in semen.

External links

• U.S. Patent 5,488,075
• Detailed information from Male contraceptives.org
• Studies of RISUG Experimental male contraceptive 1976-2004
• SMA
• ICMR Website
• ICMR 2004 Anuual Report
• Hindustan Times
• The Sperminator in Grist Magazine
• India Today Article
• Indian Express Article
• Canadian Doctor implements RISUG
• Country’s first male contraceptive aborted (October 2002)
• ICMR takes a shot at a male contraceptive (October 2000)
• An interpretation of "Status of Spermatogenesis and Sperm Parameters in Langur Monkeys Following Long-term Vas Occlusion With Styrene Maleic Anhydride"
• The Revolutionary New Birth Control Method for Men
• Male Contraception Information Project: RISUG/Vasalgel