Why you should care
Because it's a reversible vasectomy — without the surgery.
There is something of the Olympian in Sujoy Kumar Guha’s long-distance quest to bring a male contraceptive to the market. As far back as 1979 he published a study on rats in the journal Contraception but was hit with bureaucratic hurdles when he tried to move to clinical trials. Trained as an electrical engineer at the Indian Institute of Technology Kharagpur, with a doctorate from St. Louis University in medical physiology, he argues his work wasn’t taken seriously because he lacked a medical degree.
So Guha, who was close to 40 and working at IIT Delhi, went back to school. He finished five years later, with an extra year of residency. “My purpose was not to practice,” he says. He wanted the MD credential and to appear before medical committees knowing “they could not brush me off.”
Today, his male contraceptive, delivered as an injection, is one of two methods in late-stage human clinical trials –– the other is a topical hormonal gel undergoing trials in seven countries. Guha’s RISUG, short for Reversible Inhibition of Sperm Under Guidance, has completed a phase III trial in India, considered the final hurdle before a product is cleared to hit the market.
RISUG may prove to be his most well-known invention, but Guha has been tinkering for decades.
Radhey Shyam Sharma, a scientist at the Indian Council of Medical Research, is heading the clinical trials, which spanned five health centers and included more than 300 couples. After sending the results to the Drug Controller General of India (DCGI), it is expected to take around seven months for all the approvals to be granted before the product can be manufactured. Given the delays thus far, however, Sharma is hesitant to provide a timeline for getting the product to market. (The cost also remains unknown.)
The injection works by creating a plug in the vas deferens — the path sperm travels in the male reproductive system — using a polymer Guha developed. Like a vasectomy, the flow of sperm is stopped — but without undergoing surgery. “The human sperm has a head and a long tail, and it swims,” says Guha. “Studies have shown that the head of the sperm has a negative surface charge. Therefore I thought if we can bring a positive charge then it would be destroyed, or inactivated.” Unlike other methods where polymers were injected into the vas deferens, Guha’s solution is an active compound designed to impair sperm’s fertilizing ability.
“One of the reasons that men don’t use contraceptives as much as women is because there just aren’t a variety of products available,” says Professor Stephanie Page at the University of Washington School of Medicine. She applauds Guha’s “novel” RISUG technique but adds that there “is quite a lot of work to be done.”
Once the plug is in place, it can last up to 13 years, says Sharma (Guha points out that it remains effective in the first trial patient, treated around 1990). To reverse the effect, patients are injected with a solvent that dissolves the polymer. But Page questions how easily it could be reversed. “Even under ultrasound guidance, getting the needle directly where it needs to be to dissolve the plug has been much more challenging than was anticipated,” she says.
Sharma agrees that a “proper clinical reversibility study has not been done,” but it is in the planning stages and protocols are being readied. In the most recently published study on RISUG, from mid-2019 in the Indian Journal of Medical Research, several animal studies on reversibility are referenced.
Avoiding surgery is a clear advantage of RISUG; another benefit, according to the researchers, is that it is nonhormonal. As Guha explains, a man’s sperm-producing mechanism sits very near the glands that produce male hormones, which means if you manipulate one, it affects the other.
Guha, 79, is elegant, sporting a rust-colored sweater and pensive expression when we meet. He discusses his work with a sprinter’s speed, recalling exact dates and times of significant developments and saying “look here” to emphasize crucial details.
RISUG may prove to be his most well-known invention, but Guha has been tinkering for decades — starting in the 1960s when, as a graduate student, he helped design a blood-pumping device with no moving parts. He was featured in Popular Science, which proposed that the simple device could be used to silently propel submarines during warfare. In 2008, Guha drew inspiration from a cockroach’s 13-chambered heart to design an artificial “biventricular pump.” The pump is made of a series of interconnected chambers, making it less catastrophic should a single chamber fail and reducing the buildup of pressure that can be fatal in the human heart.
The inventor-scientist is well aware of the difference between crafting a method that works and one that’s safe to use over time. Still, the arduous journey between the two can make him impatient. It took several years — and roughly 24 studies — to persuade others that RISUG was safe, and trials have been stopped for a variety of reasons, including changes at the Indian Council of Medical Research funding agency. The researchers had to resort to legal intervention before trials resumed, only to see them interrupted again.
The next phase of trials — pending approval from DCGI — will focus on training health care workers to administer the injection. Guha is committed, but cautious, knowing there is a graveyard of once-promising contraceptive methods. He points to the Lippes Loop, an IUD introduced in 1962, that he asserts was distributed without adequate training and consequently failed. The upshot, Guha says, was no other implantable female contraceptives came to market in the U.S. for two decades. “Learning from that history, I would not go about it in a jump,” he says.
Perhaps, but mentally he has already made the next leap. For a version of RISUG he believes could offer protection from prostate cancer, trials have been approved in six countries. He knows there will be hurdles — but this is hardly his first race.
Correction: An earlier version of this story misattributed a quote to Radhey Shyam Sharma about the timeline for manufacturing RISUG.