For countless women, preventing pregnancy means using contraceptives that can come with serious side effects, ranging from the unpleasant to the unbearable.
But researchers are working on a different kind of contraceptive that may provide an alternative: Antibodies, which bind to and trap sperm cells so they can no longer penetrate vaginal mucus.
Though it may sound strange, the specially engineered antibodies were potent, stable, and over 99 percent effective at stopping sperm cells from moving when tested in sheep.
"Although tests in humans are needed, these [antibodies] may offer women another alternative to hormonal contraception," protein engineer and immunologist Bhawana Shrestha and colleagues write in their published paper, which describes how anti-sperm antibodies could slow down sperm cells on a mission.
"Sperm must swim through mucus and ascend to the upper [female reproductive] tract to reach and fertilize the egg," the team explains.
"Typically, only [about] 1 percent of the ejaculated sperm enter the cervix, even fewer arrive at the uterus, and only dozens of sperm (out of the ~200 million in the ejaculate) reach the neighborhood of the egg."
But it only takes one sperm to start a pregnancy.
Of the most reliable birth control methods, many are hormonal contraceptives that work by providing steady doses of sex hormones to stop eggs being released from the ovaries. The contraceptive pill, implant and vaginal ring are some examples which are very effective at preventing pregnancy, if used correctly.
Unfortunately, some users of hormonal contraceptives experience serious side effects, from weight gain and low libido to migraines and mood changes, even depression. There are also associated health risks, such as higher odds of blood clots on the pill and a slightly increased risk of breast cancer.
"There's a clear need for large-scale clinical trials into new and existing forms of birth control," write Bethan Swift and Christian Becker for The Conversation, two reproductive health researchers at the University of Oxford, who were not involved in the study.
"Yet despite this, little investment is actually put into making this happen, and priority tends to be given to other areas of research." Not all improved methods pass the bureaucratic obstacles of international regulations, either.
Funding and access issues aside, this new study, led by Shrestha at the University of North Carolina, takes a different approach to most available contraceptives. The team focuses on antibodies, the Y-shaped molecules immune cells produce to neutralize infections or foreign particles.
Some women, who are otherwise healthy but have a condition called immune infertility, produce anti-sperm antibodies in their reproductive tract that "trap vigorously motile sperm in mucus and prevent them from reaching the egg," Shrestha and colleagues explain.
Using these antibodies as a scaffold, the researchers engineered a set of souped-up antibodies by adding multiple 'binding fragments' to enhance the sperm-binding properties.
These fragments, or binding sites, latch onto a particular cell surface marker which is present on all human sperm, but absent in all other tissues and not found in females. This specificity likely makes the treatment quite safe, but way more research is needed before we know for sure.
Testing the antibodies using a 'sperm escape assay', the researchers quantified how many sperm cells could escape the traps of antibodies in a plastic tube filled with vaginal mucus.
Compared to original anti-sperm antibodies, the modified antibodies were at least 8 times better at bundling up sperm cells, preventing them from swimming freely – a process delightfully called agglutination.
The next test was injecting solutions of the antibodies, followed by human sperm samples, into the vaginas of several sheep. After just two minutes, the antibody treatment had reduced the number of motile sperm cells in retrieved fluid samples by at least 97 percent.
For potential use in humans, rather than using a vaccine to teach the body's immune system to make the antibodies, the antibodies would be delivered directly into the vagina as well.
This could be done a few ways: as a rapidly dissolving film or with "intravaginal rings (IVR) that afford steady release of [antibodies] over a duration spanning the fertility window in most women to create a contraceptive product akin to the NuvaRing but without the hormones," Shrestha and colleagues write.
"We are actively pursuing the development of an IVR that can release these [antibodies] and anticipate insights to emerge in the years ahead."
There's still a way to go yet as the strategy hasn't been tested in humans, and the study didn't examine how well the treatment might prevent pregnancies; it only counted mucus-busting sperm.
"Actual contraceptive efficacy in humans must be determined through rigorous clinical studies," the researchers note.
If the method does prove to be effective at preventing pregnancy in further trials, it might also have benefits when the job is done.
"Rather than altering physiological mechanisms underpinning fertility such as hormones, topical immunocontraception should afford rapid return to fertility, unlike the months of delay experienced by some women even after they have discontinued the use of long-acting hormonal contraceptives," the researchers write.
The research was published in Science Translational Medicine.