A no-scalpel vasectomy – via an occlusive non-hormonal hydrogel injected into the vas – has passed a preliminary clinical test, achieving near-100% azoospermia within two weeks and maintaining the status to day 30 in the first men to undergo the procedure, reported Australian scientists in their initial results of the first in-human trial.
Sperm concentration decreased by as much as 99.98% by day 14 in the first six men who underwent the procedure. After 30 days, it had decreased by 99.9%-100% in five of the six men. No serious adverse events occurred.
Designed to maintain azoospermia for more than a year, the hydrogel dissolves spontaneously, reports MedPage Today.
In animal studies, the ADAM implantation procedure blocked sperm passage through the vas for up to two years, reported Dr Nathan Lawrentschuk of Epworth Freemasons and Royal Melbourne hospitals in Australia, at the recent American Urological Association annual meeting (28 April-1 May).
“The available data have shown a favourable profile for the implantable hydrogen and suggest that the primary endpoint of the trial (safety) will be met,” he said. “All procedures to date have been successful. Patients have experienced mild and moderate adverse events, primarily related to the procedure, not the implant, all of which resolve quickly. Azoospermia has been observed in all patients with 30 days of biogel implantation, even with the lowest dose.”
Enrolment in the trial continues, and additional sites across Australia are being recruited to accelerate the trial process. Long-term plans include expansion of clinical evaluation beyond the country, he added.
Implantation occurs as an outpatient procedure, using local anaesthetic, taking about 30 minutes to complete, in which the hydrogel is injected directly into the vas via cannulation, without need for an incision.
Virginia-based manufacturer Contraline has developed an injector that connects to the cannula and automatically delivers a specified dose of the gel.
The first-in-human trial eventually will include 30 healthy men, ages 25-65, with normal semen parameters.
Participants had to agree to use an alternative form of contraceptive and be willing to accept the unknown risk of pregnancy during the study duration, Lawrentschuk said.
Sperm concentration was assessed at baseline, day 14, and day 30. Follow-up will continue for up to three years.
The first seven patients to undergo implantation had a mean age of 37.7.
The most commonly reported adverse events were scrotal bruising and discomfort, swelling around the surgical site and testicular pain. All but a few were mild and the rest were moderate. They all resolved in an average of 4.6 days, and all had resolved by day 14.
Lawrentschuk said no scarring or obstructive problems occurred during animal studies, with follow-up for as long as two years.
In the human trials, one patient was excluded from analysis because of a protocol violation. Day 14 sperm concentration assessments showed that three of the six men had achieved azoospermia (99.8%-99.98% reduction from baseline), and the remaining three had achieved azoospermia by day 30 (99.91-99.99% reduction from baseline).
Lawrentschuk said the procedure causes substantially less pain than a conventional vasectomy, and gives men the opportunity to take control of contraception.
He added that initial reaction has been encouraging, as reflected in the number of men who have inquired about enrolling in the trial.
He acknowledged, however, that investigators are not absolutely sure when the hydrogel will dissolve. The implantation remained effective for two years in animals before dissolving. Whether that will apply to men will be determined during long-term follow-up in the clinical trials. When the gel does dissolve, men should be able to repeat the procedure if they want, he added.
Study details
Preliminary results of a first-in-human clinical trial of ADAM, a non-hormonal hydrogel-based male contraceptive
Paul Anderson, Damien Bolton, Nathan Lawrentschuk.
Presented at the American Urological Association conference 2023
Objective
Since the introduction of modern contraception in 1960, the focus has been on women, with a large assortment of hormonal and non-hormonal contraceptive options available for females. In contrast, male contraceptive options currently include only condoms, vasectomy, and the withdrawal method. Here we present the initial results from a first in human clinical trial of ADAM, a non-hormonal, non-permanent, hydrogel-based contraceptive.
Methods
The preliminary safety and efficacy of ADAM (Contraline, Inc.), a highly biocompatible non-hormonal, non-permanent hydrogel designed for injection into the vas deferens, was assessed in an open-label, single-arm, prospective, multi-centre, dose-ranging clinical trial with up to 30 male subjects with normal semen parameters, aged 25-65 years. After institutional review and ethics board approval, an initial cohort of four men were implanted with the first dose and rate of the ADAM hydrogel (120 uL at 800 uL/min) under general anaesthesia at the time of this writing.
A no-scalpel vasectomy (NSV) approach was used to identify and externalise the vas deferens, followed by cannulation with a 24G over-the-needle catheter, and ADAM injection using a proprietary, automated injection device.
An additional 26 men will be implanted with variable doses pending initial safety and efficacy data. Participants will be monitored for changes in semen parameters and for adverse events for up to 36 months, or until the average of two semen analyses demonstrates 15 million sperm/mL. Men who do not achieve azoospermia within six months, and all men at 36 months, will be offered a vasectomy.
Results
A volume of 120 uL of ADAM was implantated intravasally into four men with a mean+-SD age 41.3+-7.3 years and baseline semen parameters of volume 2.15+-0.81 mL, pH 8.14+-0.13, concentration 78.45+-28.12 M/mL, motility 56.8+-7.5%, morphology 13.5+-3.7% normal forms, TMC 70.0+-15.7 M sperm. Implantations resulted in no serious adverse events within two weeks of the procedure, with post-procedure recovery characteristics similar to those in men receiving vasectomy. Post-procedure semen analyses at 14+-3 days demonstrated volume 1.9+-1.0 mL, pH 8.3+-0.2, concentration 1.1+-1.2 M/mL, motility 0.0+-0.0%, and TMC of 0.5+-0.6 sperm. Two patients had azoospermia and a third only five motile and six immotile sperm / 30 HPF in the initial post-procedure sample.
Conclusions
Intravasal injection of ADAM into human male vas deferens is feasible, and initially safe and effective at rapidly inducing near-azoospermia. Additional data will define the longer-term safety and efficacy of ADAM and its feasibility as a male contraceptive.
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Second potential male birth control pill passes human safety tests