Can therapeutic ultrasound be used as a reversible male contraceptive?

Background, Motivation and Objective: Studies on the utility of ultrasound as a reversible male contraceptive were initially reported in the 1970s by Fahim and his colleagues. Their studies with rat and human subjects showed that a single dose of ultrasound could dramatically decrease sperm count and induced infertility for up to six months. Depending upon the dose of ultrasound, this contraceptive effect was reversible. Our objective was to determine if modern therapeutic ultrasound instruments could form the basis for a male contraceptive, and to elucidate acoustic mechanism of observed infertility. Statement of Contribution/Methods: In order to determine effect of ultrasound on reproductive capacity in-vivo, rat testes were subjected to 2.2 W/cm2 ultrasound at either 1 or 3 MHz using a therapeutic ultrasound generator and transducer. Testis histology and sperm counts were examined two weeks after treatment. To elucidate mechanism of ultrasound effects on reproductive cells, sperm from rat epididymis were sonicated in-vitro in a dual optical-acoustic-focus setup with 1 MHz pulses with lengths ranging from 1,000 to 10,000 cycles. Pulses had peak negative pressures between ∼1 and 10 MPa and were delivered at a 1 Hz PRF for between 30 and 90 s. Results: Sham-treated rats produced sperm counts between 200 to 300 million sperm per cauda epididymis, while ultrasound treatment reduced sperm counts to ∼2 million sperm per cauda epididymis two weeks after treatment. Sperm recovered from ultrasound-treated rats had reduced motility. The corpus and caput epididymis of treated animals had significantly lower numbers of sperm than sham-treated animals. In addition, portions of the epididymis had decreased tubular diameters, similar to that seen in castrated animals. The height of the seminiferous epithelium in ultrasound-treated rats decreased significantly compared to sham-treated animals, due to a significant loss of testicular germ cells. Individual sperm exposed to ultrasound ex-vivo were observed to be extremely resistant to acoustic energy. In-vitro sonication of sperm up to ∼ 10 Megapascals at 1 MHz did not permanently alter their motility after pulses were delivered. However, if microbubbles were present in the solution, cavitation caused permanent and terminal disruption of the cells within the field of view. Discussion and Conclusions: Our studies using modern therapeutic ultrasound instrumentation demonstrate the feasibility of using ultrasound as a form of male contraception. However, in-vitro studies have not yet elucidated the mechanism of cell disruption. Further studies determining the kinetics of germ cell loss, direct effects on sperm, the duration of the contraceptive effect, and any long-term effects to the seminiferous, interstitial or epididymal epithelia are needed to establish the efficacy and reversibility of any ultrasound-based contraceptive.