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. RISUG is similar to vasectomy in that a local anesthetic is administered, an incision is made in the scrotum, and the vas deferens is tugged out with a small pair of forceps. Rather than being cut and cauterized, as it is in a vasectomy, the vas deferens is injected with the polymer gel and pushed back into the scrotum. 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.

Professor SK Guha theorizes 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, inactivating sperm before they initiate 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 volunteers who have been injected RISUG^{[citation needed]} — apparently due to an improperly administered injection. Out of the 250 volunteers who have been injected RISUG, 15 received the injection more than 10 years ago.
• Convenience - There is no interruption before the sexual act.
• Cost - The shot itself costs less than the syringe used to administer it, and its long term effectiveness would make it theoretically only a four or five time cost, in the entire lifetime of someone who chose to continue to be on it.
• Outpatient Procedure - Patients can leave the hospital immediately after an injection and resume their normal sex lives within a week.
• Duration of effect - According to Dr. 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.^{[citation needed]} Also, because sperm can still exit the body unimpeded, patients don’t experience the pressure or granulomas that can result from vasectomy.
• 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.

Potential hazards

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, WHO and Indian researchers say that the studies were not done according to recent international standards. Due to the lack of any evidence for adverse effects, trials were restarted in 2011.

Intellectual property

Intellectual property rights to RISUG in the United States were acquired between 2010–2012 by the Parsemus Foundation, a not-for-profit organization.

References

13.Jha, Rakhi K., Pradeep K. Jha, and Sujoy K. Guha. "Smart RISUG: A potential new contraceptive and its magnetic field-mediated sperm interaction." International journal of nanomedicine 4 (2009): 55.

External links

• U.S. Patent 5,488,075
• Detailed information from Male contraceptives.org
• ICMR Website
• ICMR 2004 Anuual Report
• ICMR takes a shot at a male contraceptive (October 2000)
• The Revolutionary New Birth Control Method for Men
• Expanding Options for Male Contraception.

Jha, Rakhi K., Pradeep K. Jha, and Sujoy K. Guha. "Smart RISUG: A potential new contraceptive and its magnetic field-mediated sperm interaction." International journal of nanomedicine 4 (2009): 55.