Bhawana Shrestha: ‘There is a highly unmet need for safe and effective non-hormonal contraception’

When the birth control pill was first invented and mass-produced for commercial use in 1960, it was heralded as a revolution in women’s reproductive rights. Women were finally able to take charge of their own bodies and exercise some form of control over pregnancies easily and effectively. The birth control pill, known widely in the West as just ‘the pill, was employed by an estimated 151 million women in 2019 all over the world, according to data from the United Nations.

Despite its ease of use, the pill never really took off in the developing world. In South Asia, female sterilization, or tubal ligation, remains the most popular method of birth control. While both the pill and female sterilization are effective means of birth control, they come with their own risks. Tubal ligation is a surgical procedure and thus has inherent dangers while the pill, as a hormonal drug, can have extensive side effects. 

But birth control is often necessary, whether it is unmarried couples who’d like to wait until they get married or married couples who’d like to plan their families. Among the nearly 8.5 million women of reproductive age (15–49) in Nepal, “almost five million want to avoid a pregnancy”, according to a 2019 study by the Guttmacher Institute. Nepalis, fortunately, have access to a range of birth control measures, ranging from condoms and pills to intrauterine devices (IUDs) and temporary hormonal injections. The most popular method of birth control, in Nepal, however, remains female sterilization, according to the Guttmacher Institute, accounting for 29 percent of all contraceptive use, followed by injectables (17 percent), condoms (10 percent), the pill (10 percent), implants (7 percent) and IUDs (3 percent). 

Injectables, the pill, and implants are all hormonal contraceptives, meaning that they inhibit certain hormones in the body to prevent pregnancy, usually by stopping the body from ovulating. The few non-hormonal contraceptives available to women — tubal ligation, copper IUDs — can be difficult and invasive. 

But perhaps not for much longer. 

Bhawana Shrestha, a microbiologist at the University of North Carolina-Chapel Hill, is currently working on an antibody-based form of non-hormonal contraceptive. In simple terms, what she’s developing is an antibody that reacts to sperm, leading them to clump together, or agglutinate in biological terms, and become non-motile, effectively killing them before they reach the ovum. Her initial research has yielded very positive results. 

This could potentially become a revolutionary form of contraception, especially as it will eliminate the side effects associated with hormonal birth control and will not require an invasive procedure. 

In an email interview with The Record, Shrestha, who also goes by Suruchi, spoke about her interest in developing a non-hormonal form of birth control and what stage her research is currently at. 

Could you tell us a little bit about yourself? Where were you born? Where did you grow up and how did you end up at UNC-Chapel Hill?

I was born and raised in a small town called Bayarghari in Syangja district. At the age of 15, like many students in Nepal, I moved to Kathmandu to complete my 11^th and 12^th grades at St. Xavier’s College. I received my Bachelor’s degree in Biochemistry from Claflin University in South Carolina, USA, where I got my first stab at performing molecular biology research, which eventually led me to pursue a Ph.D. in Microbiology and Immunology at UNC-Chapel Hill. 

What kindled your interest in researching this non-hormonal form of birth control?

The majority of contraceptives available in the market are hormonal contraceptives, which are associated with a plethora of real and/or perceived side effects such as acne, pelvic pain, mood disorders, etc. Many women also have medical contraindications to the use of estrogen-based hormonal contraceptives. I, unfortunately, suffered those side effects with the use of a hormonal IUD and contraceptive pills, leading me to not only discontinue their use within a short period but abstain from all hormone-based contraceptives. This personal experience was one of the main reasons behind my interest in developing a safe, non-hormonal method of contraception.

What is the current status of your research? You've had success when it comes to sheep. Are you going to be testing on humans? 

We observed that our multivalent anti-sperm antibodies eliminated 100 percent of progressively motile sperm within two minutes in the sheep model with a low dose of 33 micrograms, suggesting the topical use of anti-sperm antibodies could provide highly effective and safe contraception. 

We are actively establishing the processes to manufacture multivalent antibodies at a quality suitable for use in a clinical setting. We are also performing other formulations and safety studies needed by the regulatory agencies before human studies. The parent (non-multivalent) anti-sperm antibody is currently being evaluated via a human post-coital test in surgically sterilized women, which allows an early assessment of contraceptive promise without risk of pregnancy.

Would the antibodies be permanent or temporary? How would you reverse this kind of birth control if the woman in question decided to have a child?

Decades ago, the discovery of anti-sperm antibodies motivated the development of contraceptive vaccines. The vaccines elicited anti-sperm antibodies with substantial contraceptive efficacy, but the approach came to a halt due to potential concerns of infertility. Therefore, our approach is to directly deliver the anti-sperm antibodies to the vagina to achieve a potent contraceptive effect while avoiding the risk of irreversible infertility. Since our anti-sperm antibodies do not modify the physiological mechanisms behind fertility but simply reinforce the mucus barrier that is continuously secreted and cleared, our method should afford a rapid return to fertility upon discontinuation.  

Do you believe that antibody-based contraceptives are the way forward when it comes to birth control for women?

I believe antibody-based contraceptives could positively change the way women perceive and use birth control, mainly because of the safety. Antibody-based contraceptives are likely to be very safe due to the specificity of the targeting, particularly when targeted to epitopes present only on sperm/male tissues and not expressed in female tissues. Additionally, the topical delivery of antibody-based contraceptives could further increase safety because antibodies delivered to mucosal surfaces such as the vagina are poorly absorbed into the systemic circulation and the vagina represents a poor immunization inductive site. 

Would this new kind of contraceptive be useful to women in developing countries like Nepal where even birth control pills are not used commonly? 

Birth control pills are not commonly used because of the unwanted side effects incurred by hormones and the strict regimen required for the pill. As I described above, antibody-based contraceptives should be safe to use, which could increase the acceptability of this birth control method among women. Additionally, the acceptability could be further enhanced by formulating the antibodies in a multitude of ways to meet the contraceptive needs of different subsets of women. For those desiring a long-acting method, the antibodies can be formulated into an intravaginal ring that can slowly release the antibodies across the fertility window for month-long contraception. For women who prefer on-demand options, the antibodies can be formulated into a vaginal film to be inserted shortly before intercourse. Additionally, the overall approach of vaginal delivery of antibodies can serve as the basis for multi-purpose prevention technologies, for instance providing both contraception and STI prevention.  

Is there anything else you'd like the lay public to know about your research? 

It is very apparent that there is a highly unmet need for safe and effective non-hormonal contraception. However, not only has there been little to no effort in resolving this unmet need, it is hardly talked about in the scientific world. Therefore, our motivation for the study was to first highlight this unmet gap in the contraceptive field and attempt to fill the gap using potent anti-sperm antibodies for non-hormonal contraception.

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Update: The feature photo has been updated on request.