Ovulaid - Rethinking fertility tracking

Project inspiration: Ten percent of women suffer from infertility issues

According to the World Health Organization, an estimated ten percent of all women suffer from infertility or subfertility, defined as having tried to conceive unsuccessfully for five years or more¹. These issues can lead to extensive psychological problems, such as stress, depression, and anxiety, the impact of which is often overlooked². With our project, we wish to combat the issues of infertility, by providing women with an easy and practical way of tracking their menstrual cycle, so they know when they are fertile, and have a higher chance of successful conception.

Defining the problem: Ovulation and the fertile window

Women are only able to conceive during a short window of five to six days during each menstrual cycle. This ‘fertile window’ is determined by the ovulation, a process where an oocyte (a fertile egg) is expelled from the ovaries and travels through the fallopian tubes towards the uterus³. The textbook example of a menstrual cycle is commonly presented as lasting 28 days. However, research suggests that the prevalence of women experiencing irregular menstrual cycles is as high as 80%⁴, making it very difficult for most women to determine when they are in their fertile window, and thus able to conceive. Peaks of certain sex hormones, namely estrogen and luteinizing hormone (LH), can predict ovulation⁵.

Figure 1 - Hormone levels of estrogen, LH and progesterone during a regular menstrual cycle

Measuring the levels of these hormones can give women an idea of when they are fertile, even if they are experiencing irregular menstrual cycles. There are currently ovulation tests on the market, which measure hormone levels to detect ovulation. However, these tests are often impractical, as they are urine- or blood-based tests, and not precise, as they often measure only LH, giving a binary response as to whether you are ovulating or not.

Our solution: Ovulaid - Rethinking fertility tracking

Striving to create a better solution for fertility tracking, we came up with Ovulaid; a hormone-based ovulation test in a chewing gum. Using a yeast biosensor, we want to create a product that is comfortable and easy to use, and which gives a precise and comprehensive picture of the entire menstrual cycle.

Our yeast biosensor will contain receptors detecting both LH and estrogen (and potentially in the future progesterone as well), as opposed to most tests currently on the market. When the biosensor detects an increase in LH or estrogen, it will produce a colored compound, changing the color of the chewing gum according to the hormone levels. For easy use, we plan to create an app to use with the gum. Through a photo of the gum, the app will then precisely determine the intensity of the color and let the user know her fertility status. The results can be logged for future predictions of the fertile window for the individual user.

Project summary. For details, go to our subpages!

Parts | The modular nature of synthetic biology makes the assembly of functional constructs flexible and allows to tinker with different subunits. For this project, we constructed an insulated, modular system for the biosensor while parts from previous iGEM teams were characterized and improved also.

Design | The different modules necessary to realize this project were USER-cloned and assembled to individual genome integration cassette. The plasmids were amplified in E.coli, and combinations of modules were then integrated into the Saccharomyces cerevisiae genome.

Modeling | In order to assess if Ovulaid could realistically serve as an alternative to common ovulation tests, one needs to get an idea of how much hormone is required to trigger the color response. Therefore, the system was simulated in an elaborate model of 20 ordinary differential equations (ODEs).

Safety | It is important to address the public’s and the lawmakers’ concerns when dealing with genetically modified organisms. For these reasons different measures were taken, varying from the choice of the working organisms to the implementation of a kill switch in order to address the biocontainment. Furthermore, the wellbeing of each team member was ensured.

Integrated Human Practices | To find out how Ovulaid would be received and how we could best structure our efforts, we have consulted multiple experts, involved our target group internationally, and integrated concerns regarding the project. We have confronted the legal and entrepreneurial difficulties our product could face and made a business plan for further venture. To communicate our project and the need for infertility awareness, the team has reached international as well as national media coverage, and worked towards engaging and educating both high and elementary school students in Ovulaid, iGEM, and synthetic biology.

App | We wanted to design Ovulaid for people to actually use, and we have therefore put great effort into finding out how people could use it in a way that is easy, fun, and allows for precise cycle tracking. We came up with the aforementioned Ovulaid app. The Ovulaid app is an innovative cycle tracker that combined with the Ovulaid chewing gum empowers women to track their menstrual cycles and monitor their hormonal health, while also generating valuable anonymous data that, with given consent, can be shared with researchers to promote research in hormonal health.

Education and Engagement | An integral priority of Ovulaid has been to engage and educate our peers and also ourselves through outreach. Ovulaid has already been picked up by mainstream media and the project has been featured in The Guardian and the team has engaged in the ongoing public Danish debate on GMO-technologies. Besides presenting Ovulaid at different events, we are working with Biotech Academy on making a synthetic biology case to be used in high school labs.

Collaborations | In the spirit of a globally connected iGEM community, the team has hosted and attended different meetups. Further, we have helped other iGEM teams to meet their collaboration goals for instance by answering their surveys. Together with a Dutch and a British iGEM team we assessed the potential of our ideas in our countries. Finally, UCopenhagen actively works with other Danish teams on the establishment of a Danish iGEM network.

Team | Our team consists of 13 students spread across different STEM fields. We are very proud of our project and accomplishments but first and foremost with ourselves and each other.

Future Plans | The iGEM season finishes in November - But this is not the end of Ovulaid! Some of our members are evaluating the financial possibilities to continue with the development of the project. Furthermore, we hope that our project will have an impact on future developments in the field.

Attributions | While the team has been working independently throughout the project, we could not have made it without the help, support, and curiosity of all the wonderful people we have been in contact with. We would like to thank all the people that have made our journey possible, both in and outside the lab.

References

1. World Health Organization. (2019). Infertility is a global public health issue. [online] Available at: https://www.who.int/reproductivehealth/topics/infertility/perspective/en/?fbclid=IwAR3N2auePGxujtWa12XcZhSJK4FqAfumCv_NuUDOfgW_71aoVSgmd4zZOhg [Accessed 18 Oct. 2019].
2. Publishing, H. (2019). The psychological impact of infertility and its treatment - Harvard Health. [online] Harvard Health. Available at: https://www.health.harvard.edu/newsletter_article/The-psychological-impact-of-infertility-and-its-treatment [Accessed 18 Oct. 2019].
3. Wilcox, A. (2000). The timing of the "fertile window" in the menstrual cycle: day specific estimates from a prospective study. BMJ, 321(7271), pp.1259-1262.
4. Karout, N., Hawai, S. and Altuwaijri, S. (2012). Prevalence and pattern of menstrual disorders among Lebanese nursing students. Eastern Mediterranean Health Journal, 18(4), pp.346-352.
5. Boron, Walter F.Boulpaep, Emile L., eds. Medical Physiology: A Cellular And Molecular Approach. Philadelphia, PA : Saunders/Elsevier, 2009. Print.
6. National Collaborating Centre for Women’s and Children’s Health (UK). Fertility: Assessment and Treatment for People with Fertility Problems. London: Royal College of Obstetricians & Gynaecologists; 2013 Feb. (NICE Clinical Guidelines, No. 156.) 5, Initial advice to people concerned about delays in conception. Available from: https://www.ncbi.nlm.nih.gov/books/NBK327786/