Integrated Human Practices
Socioeconomic Challenges and Sustainability
Impact of the problem
Endometriosis is a disease characterized by the presence of tissue, similar to the type that lines the inside of the uterus, which grows outside of the uterus and on other organs in the abdomen (Dunselman, et al., 2014).
Endometriosis affects more than 10% of women globally, which is more than 200 million women in total, and this doesn't even account for cases within the LGBTQIA+ community (Dunselman, et al., 2014). Symptoms include chronic fatigue, excessive menstrual bleeding, painful bowel movements, burning urination, inflammation, scarring, infertility and may damage the nearby organs and tissues. Patients with endometriosis also tend to have more sensitive vaginal canals which lead to pain during intercourse, and even when inserting tampons or menstrual cups (Bese T, et al, 2003). Despite experiencing these symptoms throughout most of their lives, both endometriosis patients and healthcare professionals often fail to recognize that they are signs of this chronic disease. (Dr. Ashley Gubbels, July 2020, Personal Interview).
Even with endometriosis prevalence and severity, there are currently more than 11% of patients with undiagnosed endometriosis around the globe [Louis, G. M. B., Hediger, et al, 2011]. There are no current diagnostics available except for exploratory surgery, such as laparoscopy, or auxiliary imaging methods like ultrasound (Manero, et al, 2009). The current diagnostic methods are either invasive, expensive, require the involvement of professionals, or do not have sufficient specificity to allow for a definitive diagnosis of endometriosis and need multiple evaluations for proper confirmation (Kinkel., et al., 2006). The conclusive diagnosis of endometriosis can be reached only by laparoscopy, an invasive surgical procedure (Pavone, M. E., et al., 2009).
As we performed research and interviews with stakeholders, we found that an early, reliable, accessible, and non-invasive diagnostic method would allow professionals to diagnose endometriosis in patients within a narrower window of time after the onset of symptoms. Thus, avoiding an extensive number of unnecessary invasive diagnostic and therapeutic procedures and years of unresolved, unbearable pain. This early detection could help patients take advantage of the earlier reduction of disease burden, improvement of fertility, and prevention of progression of the disease (Signorile, P. G., & Baldi, A. 2018).). Therefore, we conclude that the development of a non-invasive, accessible, and reliable test for endometriosis is both responsible and good for society.
From literature research, we confirmed that there is a lack of awareness in both the general public and medical professionals which further leads to the lack of research about endometriosis, funding for the research, and a lack of new technology that helps the diagnosis (Moen, M. H, 2017). Because of this, there is a delay of diagnosis up to 10 years (Bese T, et al, 2003 ). Therefore, more educational material and campaigns are urgently needed in order to help the patients understand and improve the patients' treatment-seeking abilities.
“The sooner the patient is diagnosed, the sooner they get appropriate treatments and their pain under control. And the cost of the treatment could decrease. ” (Dr Ashley Gubbels, July, 2020, Personal Interview)
As a chronic disease, endometriosis symptoms and the disease progression get more severe over time. The symptoms could start from pelvic pain then progress to excessive menstrual bleeding and painful urination or, in extreme cases, even infertility and ovarian cancer (Ballard, Lowton, et al, 2006 ). Given this disease progression, the earlier the patients can get diagnosed with endometriosis, the easier it becomes to manage the disease with less treatment cost and more treatment options (Dr Ahsely Gubbels, July 2020, Personal Interview).
Laparoscopy is the gold standard of diagnosis. During a laparoscopic procedure, a long, thin viewing instrument, called a laparoscope, is inserted into the abdomen through a small, surgical incision. This allows the doctor to view the endometrial tissue or take a tissue sample (Duffy, J. M. N., et al., 2014).
Other methods including a pelvic exam, ultrasound, and magnetic resonance imaging (MRI) cannot confirm the occurrence of endometriosis without the additional testing provided by laparoscopy. These other methods are typically used to help with surgical planning.
Pain Medication: pain relievers such as acetaminophen and ibuprofen are recommended for endometriosis patients to temporarily reduce the pain.
Advantages of pain medication (Eases endometriosis-associated pain) [Institute for Quality and Efficiency in Health Care, 2017]
Disadvantages of pain medication (May increase the risk of heart attack, stroke, stomach or intestinal bleeding.) [Proctor, M., & Farquhar, C., 2006)]
Hormone Therapy (Mayo Clinics, 2019)
Birth control pills and vaginal rings help control the hormone that is responsible for the endometrial-like tissue build-up each month.
Advantages of hormonal contraceptives (Hormonal contraceptives are highly effective in reducing women’s chances of getting pregnant. Additionally most of the contraceptives reduce menstrual bleeding, pain associated with menses) [Weisberg, E., & Fraser, I. S. (2015).]
Disadvantages of hormonal contraceptives (Some hormonal contraceptives may cause the formation of functional ovarian cysts.)[Weisberg, E., & Fraser, I. S. (2015).]
Gonadotropin-releasing hormone (Gn-RH) agonists and antagonists:
These drugs block the production of ovarian-stimulating hormones, lowering estrogen levels and preventing menstruation.
Advantages of Gn-RH agonists and antagonists ( Gn-RH agonists and antagonists therapy causes endometrial tissue to shrink, reduces menstrual bleeding and hormonally-related pain) [Rafique, S., & Decherney, A. H., 2017]
Disadvantages of Gn-RH agonists and antagonists (Gn-RH agonists and antagonists may reduce fertility during treatment and decrease libido; also the treatment can cause insomnia, headaches, mood swings, and long term memory issues even after discontinuation.) [Magon N., 2011]
Aromatase inhibitors are a class of medicines that inhibit the extra-ovarian synthesis of estrogens. Estrogen levels are considered to be the potential modulators in the pathophysiology of endometriosis because estrogen stimulates lesion development in endometriosis. [Shao, R., Cao, S., Wang, X., Feng, Y., & Billig, H. (2014)]
Advantages of aromatase inhibitors (Aromatase inhibitors have been shown to decrease pain and reduce the size of extrauterine endometrial lesions.) [Słopień, R., & Męczekalski, B. (2016)]
Disadvantages of aromatase inhibitors (Aromatase inhibitors can only be used by a limited population of endometriosis patients. This includes women who have undergone menopause, people who are in natural menopause or medication-induced menopause or those who do not have ovaries.) [Słopień, R., & Męczekalski, B. (2016)]
Progesterone Intrauterine Device (IUD) is inserted into the uterus in order to prevent and treat heavy menstrual periods.
Advantages of IUD ( IUD reduces menstrual bleeding and cramps.) [Institute for Quality and Efficiency in Health Care, 2017]
Disadvantages of IUD (IUD may increase the risk of heart attack, stroke, stomach or intestinal bleeding. May affect mood and appetite. It also needs to be inserted by a healthcare provider. Upon insertion, IUD may cause mild irritation for the first few months and even infertility later.) [Dhamangaonkar, P. C., Anuradha, K., & Saxena, A. (2015)]
Hysterectomy is a surgical procedure during which the uterus is removed.
Advantages of hysterectomy (Hysterectomy may reduce pain, lower total treatment costs, and lower morbidity.) [Pillarisetty LS,2020]
Disadvantages of hysterectomy (Recurrence of endometriosis symptoms could still happen.) [Rizk, B.,2014.]
Laparoscopy with ablation or excision is typically used to diagnose endometriosis and endometriosis remove lesions or scar tissue.
Advantages of laparoscopy (Only a small incision is required to confirm diagnosis and treatment can be carried out at the same time.) [Farquhar C.,2007]
Disadvantages of laparoscopy (Laparoscopic surgery requires expensive equipment, meaning that not all hospitals can offer this treatment option. Also, laparoscopy requires skilled surgeons; gynecologists do not qualify in terms of expertise to fully treat the disease.) [Zanelotti, A., 2017.]
Our project goals are to reduce the cost and risk of an endometriosis diagnosis. We plan to accomplish these goals by creating a non-invasive, affordable, and reliable method of diagnosis which utilizes menstrual effluent and to create a variety of educational materials to raise people’s awareness about endometriosis.
Menstrual effluent is the ideal sample for the detection of endometriosis as it allows for non-invasive collection methods and has been shown to contain reliable biomarkers for this condition due to it containing shed endometrial cells (Nayyar et al., 2020, Warren et al., 2018). As opposed to peripheral blood samples, which can be collected at any stage in the menstrual cycle, using menstrual effluent ensures that specimen collection only occurs during menstruation, which minimizes the risk of hormone-related fluctuations in biomarker levels (Warren et al., 2018). Therefore, the use of menstrual effluent will allow us to create a fast and reliable diagnostic panel for endometriosis, while also employing a novel early and noninvasive detection technique. Earlier diagnosis of this chronic disease can then help inform patients on treatment options and prevent severe disease progression, which can include debilitating pelvic pain and infertility (Unger et al., 2011). Furthermore, individuals suffering from endometriosis have been shown to have increased positive health outcomes with increased knowledge of the disease, this usually occurs once a patient is diagnosed and has an increased sense of control about their future health outcomes (Holicov et al., 2015).
In order to collect the menstrual effluent samples, we designed a special menstrual cup for endometriosis patients. During both the literature review and from our discussions with professionals, we learned that patients with endometriosis have heavier flows (Shreya, 2016), meaning on average they use more than 2,400 feminine hygiene products per year (Shreya, 2016), and that they have more sensitive vaginal canals, meaning they feel more pain during tampon or menstrual cup use (Diva Cup, Interview with Sophie Zivku). Therefore, to tackle these problems, we created a customized 3D-printed menstrual cup that is easy to use, reduces leakage during the pullout process, offers better comfortability, and is more sustainable for the environment compared to other feminine hygiene products (i.e. pads and tampons).
Additionally, early in our research and development period, we received outstanding advice and guidance from Dr. Ashley Gubbels, a gynecologist and gynecological surgeon who specializes in chronic pelvic pain conditions such as endometriosis, interstitial cystitis, pelvic muscle pain, and neuropathic pain conditions. In our discussions with her, we discussed a sustainability problem: endometriosis patients need to use significantly more feminine hygiene products compared to healthy people due to heavier flow. This means they produce more waste overall and are at a higher risk of a bacterial infection - even though it is typically rare (Mitchell, M. A., Bisch, S., et al., 2015). Therefore, we incorporated ideas to improve both safety and sustainability for our project and menstruating individuals from the very beginning of our diagnostic development.
To create a strong societal impact, our team has been in contact with gynecological and endometriosis specialists, menstrual cup and endometriosis foundation corporate representatives, endometriosis advocates, local K12 teachers, and college professors. Each group suggested effective ways to create awareness and indicated where the development of educational materials and tools would be very beneficial. These stakeholders helped educate us about their purpose, viewpoints, the needs in the United States and around the globe, and their expectations about an ideal endometriosis detection method. A particularly striking conversation with Dr. Gubbels, an endometriosis specialist, informed us that patients are often exceptionally grateful when a physician listens to them about their symptoms and pain. We hope that our development and implementation of important educational materials regarding reproductive health and endometriosis will help facilitate a dialog between all menstruating patients, their physicians, and their loved ones.
At the same time, we strived to make our work as inclusive as possible. For example, we have posted weekly endometriosis facts to our social media accounts that have been translated into Spanish, Dutch, Mandarin, Lithuanian, Japanese, Arabic, and French, allowing us to reach a larger, more diverse audience. In addition to these posts, we have content in American Sign Language and an emphasis on the artwork to explain concepts for the Deaf community in the United States, as well as alternative texts for our work with detailed written descriptions for those with visual impairments.
Overall, with the help and guidance of our stakeholders across the globe, our team has created a comprehensive model for the non-invasive detection of endometriosis and has developed educational materials and tools to bridge the gap in knowledge about this chronic disease for both patients and physicians, all while taking sustainability, comfort, ease, and inclusivity into account for our values and goals.
Gynecologist – Dr. Gubbels
Dr. Ashley Gubbels is a fellowship-trained minimally invasive gynecologic surgeon. She specializes in chronic pelvic pain conditions such as endometriosis, interstitial cystitis, pelvic muscle pain, and neuropathic pain conditions.
[Endometriosis patients] are really touched when they find someone that just listens and takes them seriously… and that’s really heartbreaking.” Ashley Gubbels,MD
We wanted to know about what is missing in the current chain of treatment for endometriosis and where we could improve with our project regarding biology, menstrual products and educational materials.
Prior to the meeting with Dr. Gubbels, we wanted to contact insurance companies to advocate for improvements in insurance coverage for endometriosis patients. Dr. Gubbels said that several endometriosis treatments are covered by insurance, but not all. For example, newer drugs such as lupron are not covered by insurance. Dr. Gubbels agreed that it would be a substantial improvement in endometriosis patients’ health if insurance companies covered more endometriosis treatment options. However, we learned that this procedure would be complicated because we would need to provide evidence that early diagnosis leads to lower costs for the insurance company. With this in mind, we came to the conclusion that advocating for changes in insurance companies would be out of the scope of our project due to the short timescale and lack of data availability from insurance companies.
Although learning that attempting to change insurance plans for endometriosis patients would be difficult and may not be possible due to the time limits of the project, Dr. Gubbels emphasized that it is worth focusing on educating health professionals to improve the treatment outcomes for endometriosis patients.
We learned the importance of educating teenagers and physicians (especially family medicine and pediatrics) about endometriosis as there is not enough accessible material presented targeting these two groups. We decided to create educational materials, which included infographics and brochures that contain information about endometriosis that targets both the general public at different ages and medical professionals.
Industry - Diva Cup - Sophie Zivku
Sophie is the Corporate Communications Manager at Diva International Inc, one of the largest corporations that manufactures menstrual cups and is also devoted to women rights.
Industry - Diva Cup - Sophie Zivku
We wanted to learn more about hardware design of the menstrual cup, especially relating to endometriosis patients. We also wanted to know their opinion about the necessity of a sterilizer, and gain insight into what should be highlighted in our educational materials.
We learned that one of the worst problems with endometriosis is indeed education, especially when relating to the physicians (Sophie Zivku, July 2020, Personal Interview). Physicians are often ill-informed in regards to female reproductive health, resulting in them disregarding endometriosis pain as the patient exaggerating their period pain. This can lead to patients avoiding physicians and specialists, resulting in increased length and severity of symptoms and the realization that their symptoms are indicative of endometriosis, resulting in a late diagnosis (Sophie Zivku, July 2020, Personal Interview). Physicians’ lack of understanding of endometriosis symptoms and diagnosis contributes largely to the delay in endometriosis diagnosis. We also learned how people, in general, do not know enough about their body and anatomy, especially their reproductive system, as it was not emphasized enough in the education system (Sophie Zivku, July 2020, Personal Interview). Therefore, educational material is desperately needed, especially among physician populations and women who have not received a proper education.
Additionally, we learned that endometriosis patients often struggle with menstrual cups because of muscle spasms and severe continuous pain. Diva and other menstrual cup companies provide models with dimensions more suited to the altered physiology of endometriosis patients (Sophie Zivku, Personal Interview, July ). We also discussed the need for cleaning the cup thoroughly after use and Ms. Zivku agreed that using a UVC sterilization might increase the access to menstrual cups for patients and consumers in areas without proper access to clean water, whether permanent or temporary (i.e: camping). Other conventional cleaning methods (i.e. boiling, castile soap, commercial cleaners) are sufficient for sanitation, but are less accessible for areas with limited access to clean water. In other words, this sanitation method will ensure the cleanliness of the product and will reduce water use, providing a more sustainable alternative for the user and environment.
That being said, Sophie was in favor of the concept of using menstrual cups as the collection method for the menstrual effluent, but addressed that the cup would not be stable for transport without risking spilling or leakage. This inspired the use of a syringe to transfer collected menstrual effluent from the cup into a vial that can be transported to a lab for testing. She also stressed how this is a more sustainable method, as the menstrual cup, made of medical-grade silicone, requires minimal chemicals, water and plastic during production, and can be reused up to 10 years ( OrganiCup, 2020). These factors will ensure greater safety and sustainability to both users and the environment (Eijk, A. M. van, Zulaika, et al., 2019; Lemaire, G. S., 2006 ).
Patient - Heather Guidone
Heather is the Surgical Program Director for the Center for Endometriosis Care, Atlanta, GA. She has a personal history and diagnosis of advanced endometriosis. Heather has worked in the endometriosis community for nearly 30 years, garnering an international reputation for her tireless efforts to advance various clinical, advocacy, legislative, media, research, education, and policy initiatives on the disease.
Patient - Heather Guidone
We wanted to know what she feels is in need from a perspective of a patient herself and as an advocate for endometriosis education.
Heather shared with us her story as an endometriosis patient. She shared how she was misdiagnosed for years as she did not have enough knowledge about endometriosis and that her health professionals never talked about endometriosis as a possible cause of her symptoms. For individuals in areas with fewer medical resources, it could take them years to be properly diagnosed (Farland, L. V., & Horne, A. W., 2019.). She helped us confirm that a more rapid, accessible, and non-invasive diagnosis, as well as better educational materials, are all needed. The team met with Heather on July 16th where we introduced our endometriosis education project to her and received positive encouragement and support. She told us she was absolutely thrilled to hear a team working raising awareness for endometriosis and that she was committed and onboard in helping and assisting us. She happily agreed to review our educational content. She even graciously offered to promote the materials we would develop in the Endometriosis Research Center once we completed them. During the meeting and the emails we exchanged later, Heather provided constructive feedback on the infographics and brochures we created. Based on her suggestion, we corrected the inconsistent/incorrect definition of the disease on different pieces and the updated data. The materials went through several revisions until both the team and Heather were pleased with the result.
Mr. Curtis Birthwright and Ms. Kathryn Frank are grade 5 teachers in John Walton Spencer School #16, in Rochester, New York. Both teachers have extensive knowledge and experience teaching elementary school students.
We initially contacted them for asking advice and feedback on developing effective teaching material on science outreach for the students.
We were sincerely touched and inspired by the enthusiasm and determination Mr. Birthwright and Ms. Frank shared in delivering quality educational material to the students. In the meeting, we learned that there is a need for teaching middle school students synthetic biology and biology in general as it is a topic that is not commonly covered in the school curriculum. They made us realize the potential of creating interesting experiments for young children to spark their interests in science. “The most important thing,” stated by Mr. Curtis, “is showing children what they CAN do with science.” As college students, we are also the role models for school-age children and our interaction with the students might motivate them to pursue a career in the STEM field in the future. We wanted to create positive and valuable memories with the students, letting them remember how fun and intriguing science can be. We also learned about the difficulties both students and faculty have experienced during COVID-19 which differ from the experiences we have as college students during this pandemic. Mr. Curtis mentioned that zoom classes are not as engaging as classrooms and students easily get distracted. It is also difficult to teach and ask students to mute themselves while others are speaking. We were informed that each student will receive a chrome book, meaning each student will have access to an electronic device to use for their classes and classwork. This will make our online teaching session more inclusive and accessible. The team also learned various valuable techniques on how to design and teach the lessons to maximize engagement with the students in an online format, such as incorporating a rewarding system, limiting the lesson time to be less than 30 minutes and to avoid teaching more than 22 students. Through our collaborations with Mr. Birthwright and Mrs. Frank, we were able to design modules about synthetic biology that would stimulate a student's interest in the STEM field.
Foundations - Endo UK
Endometriosis UK (EUK) is an organization that aims to provide support service, information, and a community for people affected by endometriosis, mostly in the United Kingdom.
Foundations - Endo UK
We wanted to know how we can help each other reach a wider audience to promote social awareness of endometriosis and what challenges are faced by endometriosis patients in the UK.
We learned from them that there is a common misconception of endometriosis: people believe endometriosis ends after menopause. We dedicated one of our weekly facts to explain to address this misconception. In addition, they helped us understand the gaps in education about endometriosis in the UK. Endometriosis UK (EUK) mentioned that most people face a challenge of diagnosis and treatments due to the lack of pathways put in place to learn about the options and impacts of various approaches. Many patients do not want to go on long term hormonal treatment because they are concerned with the adverse long term effects of them. As a result of this reluctance for hormonal treatment, patients may instead choose to learn to live with symptoms instead of receiving the proper intervention(s). Part of the challenge of country awareness stems from the lack of research and funds put towards endometriosis. EUK agreed to help us reach a wider audience by sharing our project on their social media, reviewing our material with members from the support groups run by patients.
Foundations: Endometriosis Union - Denmark
Endometriosis Union is a Danish non profit association in Denmark. This organization seeks to support women with endometriosis through its own funded scientific research in endometriosis, collaborative initiatives with doctors, and by providing endometriosis patients with access to clinical and alternative treatment options for the disease.
Foundations: Endometriosis Union - Denmark
We wanted to know how endometriosis foundations function in different countries, especially on different continents.
Our team met with Sandra, a representative of the Endometriosis Union. According to Sandra, the Danish health care system is not effective in educating patients about endometriosis due to the lack of awareness of the disease among physicians. For those diagnosed with endometriosis, Endometriosis Union first encourages the patients to focus on alternative ways, such as diet changes and increased physical activity, to lower the effect of the disease rather than immediately choosing invasive treatment. After the commenting, we decided to incorporate not only the medical treatments, but also mindful training, diet, physical activity recommendations in our educational material to help the patients improve their mental health when the medical treatment might not be immediately available or effective.
Sustainability organization - RITVA
RITVA is a non-profit organization led by young sustainable menstruation activists with a nationwide network of volunteers in India. They are working towards women empowerment by creating a healthy and taboo-free space for menstrual awareness. They have worked continuously towards their mission and educated around 45,000 women about menstrual hygiene and the importance to shift towards sustainable menstruation by using reusable pads.
Sustainability organization - RITVA
We wanted to know if our approach to improve the current design of menstrual cups and increase awareness about menstrual hygiene and endometriosis is considered sustainable.
We learned from them that our approach with the menstrual cup for menstrual blood collection and daily hygienic use was indeed one of the most sustainable approaches by its reusable nature. Furthermore, they emphasized the importance of educating people about menstrual cups. What is hindering people from using a menstrual cup is that they are afraid of it due to its size. By educating people about menstrual cups, we hope to make menstrual cup usage less scary and more prevalent with menstruating individuals.
Industry - Pixie Cup - Amber English
Amber English is the Co-Founder of Pixie Cup Inc, a feminine hygiene company producing menstrual cups and different cup cleaning and sterilizing products as well as supporting women’s rights.
Industry - Pixie Cup - Amber English
We wanted to know what she feels about the topic of menstrual cup sterilization methods and users' opinions about the product
We learned that one of the biggest importances of sterilizers is that they facilitate cleaning a menstrual cup. This is a crucial point because one of the biggest reasons behind the reluctance of consumers to use the cups is due to the fact that it takes more than 20 mins and needs to clean the pot that boils the cup. If we provide them with a practical and less time-consuming solution, they are more likely to use it. As such, the biggest importance of UV light sterilizers becomes the convenience and practicality of having a portable cleaning solution. We also learned more about silicone grade menstrual cups’ durability, engineering designs that are considered for the sterilizer, and the preference of using UV-C light. Finally, Ms. English shared how the best method of promoting menstrual cups and their sterilization methods heavily depends on education and trust and recommendations. This is why menstrual cup companies tend to stress and prefer collaborating with influencers.
A feasibilty analysis was conducted after consulting with the stakeholders initially.
Social media is a powerful tool to engage with a vast and diverse audience across the globe. We decided to use social media as our approach to spread awareness about endometriosis and synthetic biology. We use Instagram (@ur.igem.2020), Facebook (@igem.rochester.2020), and Twitter (@ur_igem) with the tags #Endometriosis, #EndEndo, and #Endo5KiGEM to help spread awareness about endometriosis and our project. We posted endometriosis facts daily with them translated into multiple languages (Arabic, Chinese, French, Hebrew, Lithuanian, Spanish, and Japanese) to increase accessibility and the audience reached. Furthermore, we used our social media platforms to announce activities such as collaborations with various endometriosis foundations. Endometriosis Foundation of America partnered with us for a 5K fundraising event with the goal of raising endometriosis awareness and raising money for the foundation and our project. We also uploaded our synthetic biology educational material for high school students, Upward Bound, on Youtube, and used social media platforms to spread awareness about it. In addition to posting weekly endometriosis facts and promoting Upward Bound, we used our social media to highlight collaborations with other iGEM participants, allowing us to spread awareness about synthetic biology and the creative initiatives that iGEM encompasses. We have hundreds of followers from our university, other universities that participated in iGEM and the general public across all platforms.
"Until a cure or more effective treatment option is available, the main issue relates to taking women's experiences of severe pain seriously, and providing them with evidenced-based information about how best to manage/treat their symptoms as things currently stand." - Sally King*
*Sally King is the director and founder of the Menstrual-matters.com website. In 2013, Sally started researching the role of the menstrual cycle in ill health after experiencing unexplained nausea and vomiting, and then developing asthma after taking hormonal medication to deal with this issue. Her popular blog looks at how menstrual taboos and gender myths directly contribute to ‘bad science’, inadequate medical knowledge and training, and wider social inequalities. She is currently also doing a Ph.D. in Medical Sociology at King’s College London. Sally King provided the team with great insights and stressed the importance of educating both the public and physicians about endometriosis.
When the team had our first meeting with Dr. Gubbels, she stressed the importance of educating teenagers and physicians (especially family medicine and pediatrics) about endometriosis as there is not enough accessible material presented targeting these two groups. As the team continued to meet other collaborators, such as Endometriosis UK, Heather Guidone from the Center for endometriosis Care, the same topic and issue were kept bringing up: the lack of awareness and education about endometriosis.
We created educational material including infographics and brochures that contain information about endometriosis. These materials were split into five categories: (1) general woman's health information, (2) endometriosis education for adolescents (3) for adults, (4) for post-menstrual individuals, and (5) for health care providers. The materials were reviewed and revised in multiple rounds by different sources to ensure the credibility and quality of the information. The team then contacted and collaborated with various organizations and campus resources such as the University of Rochester Medical Center, Center for endometriosis care, University Health Service of the University of Rochester, Endometriosis Foundation of America to advertise and distribute the materials. We were fortunate to be part of this process along with many other groups and organizations to help raise awareness about endometriosis and we hope our effort will be meaningful and beneficial to the community long term.
Synthetic Biology Outreach
Another approach to engage with the local public and create awareness was by designing an online synthetic biology curriculum. This online module-based class is also uploaded to YouTube, and is, therefore, more accessible for individuals and students in areas with limited educational resources. Over the summer, we collaborated with the Upward Bound Math/Science program, one of the eight programs in the Federal TRIO Program. It is designed to provide activities and academic programs that support and challenge low-income Rochester City School District high school students in their efforts to gain math and science skills as well as applying and gaining admission to college. We created nine modules for high school students participating in the Upward Bound Math/Science program. The modules include 1-2 reading materials as a pre-assignment and then 10-15 minutes lecture followed by at-home activities and questions that help students strengthen their understanding of the material and concepts illustrated in the modules. The detailed topic, an overview of the course and other related topics are listed below in the Upward Bound syllabus. All the videos are also posted on the URiGEM YouTube video channel.
Language and Art
Scientists, as professionals, have the responsibility to engage with the public and successfully communicate science (Lorno et al. 2018). In order to engage with a wider audience, we translated Endometriosis facts and promotional video into a total of more than 11 languages, including ASL, and collaborated with other iGEM teams and our local Deaf community in the process. These translations allow us not only to include more people from all over the world but also members of the American Deaf community. In addition, we capitalized on using Art as a common language to express science through creative media including but not limited to drawing, dancing, and music. This idea is reflected through the recent gravitation towards inclusion of graphic abstracts in scientific papers because it increases audience understanding and leads to enhanced attention and ability recall of information (Yoon et. al, 2017). Members of other iGEM teams, the general public, and students of various synthetic biology outreach initiatives designed several SAA projects to share their knowledge and interpretation of science.
We interacted directly and indirectly with communities affected by endometriosis and who would influence our project. We tried to understand and integrate every stakeholder’s viewpoint about the issues surrounding endometriosis patients, diagnosis, treatment, and education. We incorporated their comments, suggestions, and improvements about the biomarker selections, educational material, SAA ideas, and hardware designs. We asked their opinion about what an ideal endometriosis detection product would consist of and what we should take into consideration for it. We aim to integrate as many comments and suggestions as possible into our project so that the developed endometriosis detection method is efficient and user-friendly.
We realized that without an in-clinic option for a non-invasive diagnosis, an at-home diagnostic would not be the most useful application of our research on biomarkers. An in-clinic option would allow for more precise measurement as well as address the lack of education on female reproductive healthcare amongst general practitioners. With this in mind, we asked our collaborator, Dr. Gubbels, if she would recommend we move forward with an at-home or in-clinic design.
Dr. Ashley Gubbels recommended that an in-clinic diagnostic would be useful, as it could influence physicians to become more knowledgeable about endometriosis and help patients receive diagnostics more quickly. After this advice, we adapted our design to work in a clinical setting by including more advanced techniques for biomarker isolation. We also took the limited equipment present in most clinics into consideration to extend diagnostics to general practitioners instead of requiring a visit to a highly trained specialist.
After we made based on literature reviews, Dr. Gubbels provided us with constructive and valuable feedback about our research, brochures, and infographics about endometriosis. For example, since children might be too young to fully comprehend endometriosis and to be informed about reproductive health, we instead chose to target the general public for these topics since it would be more beneficial and raise more awareness. She also suggested that we should include the LGBTQIA+ community in the educational material to clarify the misconceptions and biases about endometriosis in the public such that people may think transgender people do not have the risk of having endometriosis. We talked with Transgender Care at the University of Rochester Medical Center and designed a section based on the limited research papers and online authoritative sources for the LGBTQIA+ community. We also talked with Dr. Benjamin, the board-certified gynecologist at the University of Rochester. She also stressed the importance of including information for the LGBTQIA+ community. Through the help from Dr. Gubbels and Dr. Benjamin, our team was able to create content that is accurate about endometriosis and meaningful to the LGBTQIA+ community.
Dr. Gubbels also informed our team about how endometriosis patients tend to not use menstrual cups due to muscle spasms and altered anatomy in the vaginal canal causing continuous pain (Dr. Gubbels, Personal Interview, June). This inspired our hardware team to design a cup with a smaller diameter but at the same time trying to increase the depth because we learned that endometriosis patients can fill a cup much faster than the average consumer (Sophie Zivku, Personal Interview, July). We also learned that the sample size needed to perform such a test would not typically exceed 5ml which is very easy to obtain from endometriosis patients (Kamiyama, S., et al, 2004). This gave us insight that we could use a syringe for blood transportation from the menstrual cup instead of carrying all the blood in the menstrual cup.
Dr. Martin Rudnicki
Dr. Martin Rudnicki is a clinical professor at the University of Southern Denmark. Dr. Rudnicki suggested having a person who has endometriosis explain all of the information in relation to their personal experience. He said that many teens with endometriosis feel alone and have no one to talk with when they suffer from the disease. So, it is nice to have them see other people with similar symptoms and sufferings. These teens might not want to read long articles, instead, he said we should post interviews on social media that may grab their attention. Therefore, we decided to include a personal story from one of our team members, featuring a patient talking about endometriosis.
My name is Meghan Martin. I am 20 years old and I have endometriosis.
I have always had heavy periods. This started when I was 11 years old. I would change my pad or tampon almost every hour and couldn’t sleep through the night without bleeding through a pad. It took my mind away from class wondering if there would be blood on my seat when the bell rings. During soccer games, I’d dread the days we wore white shorts at away games wondering if I would be able to find a bathroom at half time after my coaches’ speech and make it back for the beginning of the second half.
I’m also tired all the time. No matter how much sleep I get, I am always ready for a nap and feel like I can fall asleep wherever I am. But I could deal with that.
The pain was what made my period unbearable. While middle school was accompanied by cramps and back pain, my experiences in high school reflect my endometriosis story the best.
In high school, I played soccer in the fall and ran distance for track in the winter and spring while playing more soccer with my club team. I loved school, was doing well in my classes and had supportive, amazing friends that I am still close with four years later. I was eating well, intensively active for about 15 hours a week, and considered myself both physically and mentally healthy. But three weeks out of the month, I was in pain.
On the average weekday, I’d go to school, track practice, soccer practice, nap, and do homework or hang out with friends. The pattern stayed the same almost every day, but the pain I experienced depended on my menstrual cycle. During the week of my period, my cramps were so bad, I’d vomit almost every time I’d exercise. I’ve worn body heating pads to get through gym class and was dependent on Pamprin (an over the counter pain medication) for practice and the school day. After participating in soccer and track for the day, I would come home and lie flat on the ground until my back stopped spazzing. I then transitioned to laying in my bed to do my schoolwork because it was the only comfortable position. But this comfort also often led to me falling asleep during my homework because the more pain I was in, the more fatigue my body felt.
I considered the second week of my cycle residue period pain. The back pain was similar, but cramps did not require a heavy dependence on Pamprin. For the third week, the back pain and cramps intensified again mimicking my period, this time only with less nausea. The fourth week was peaceful for the most part. A calm before the storm. Then I would get my period again. This cycle continued for years.
I was stubborn when I dealt with my period, not letting it stop me from doing anything, but it came with a toll. I learned how to cope with the pain but not how to thrive. By the time I made it to senior year, I was burnt out from ignoring the pain and putting extra effort into most days to learn in school and enjoy athletics. With all the hard work and determination I had put into being an athlete and my education, I no longer wanted to be a college athlete, something I’ve dreamt of since I was a little girl.
My mom didn’t give up on my dream though. Even though I had accepted my periods and how they affected all aspects of my life, my mom knew something was wrong. She knows that I have a high pain tolerance and wouldn’t be complaining of something unless it was bad. She jokes about how when my brothers and I were growing up she could almost always catch swimmers’ ear before it started for my brothers but would never know about mine until it was a double ear infection. She did some googling, as the self-proclaimed internet doctor she is, and determined I had endometriosis. Frustrated and tired, I told her she was crazy. There is no way I had some random disease that I have never heard of before after multiple gynecologists told me that it was normal. Everyone gets cramps.
During those gynecologist visits, I was asked: how painful were my cramps? I never knew how to answer. Yeah, they were painful, but when I started to express that I was in pain, I remember the doctor questioning my answer. They asked how is it possible to run 8 miles before soccer practice if I was in that level of pain? Why didn’t I miss school because of the pain? The more they probed at my lifestyle, the more I doubted myself. Maybe I was overreacting.
Looking back, I could have easily answered that I was stubborn and had a high pain tolerance, but as a teenager, I did not have the confidence to advocate for myself when I thought periods are supposed to be painful and my doctors were not supportive of my initial concerns.
Lucky for me, I get my stubbornness from my mother. She wasn’t willing to give up. She dragged me to an endometriosis specialist and about six months later, during finals week senior year of high school, I got laparoscopic surgery where I was diagnosed with endometriosis and my lesions were removed.
I had made the hopeful decision right before my surgery to attend the University of Rochester following graduation and play soccer there, hoping surgery would solve my problem. Now, as a senior at U of R, I am grateful to be a captain of my soccer team, to grow in an academically challenging environment, and most importantly to have nearly pain-free periods.
Being diagnosed with endometriosis allowed me to physically and mentally pursue my interests and passions. It changed my perspective on pain and taught me that even if I think it is just in my head or since I can’t see it, doesn’t mean it’s not there.
I am fortunate to have caught my endometriosis as a teenager. But that does not mean my story ends there. There are still some residual effects of my pain and nerves that come with the uncertainty of endometriosis returning and feeling of dread every time I need to take pain medications for cramping. Will I be able to have kids later on and will they have to endure endometriosis too? Will my constant fatigue ever subside? Why is so little known about the disease?
Endometriosis had such a big impact on my life for years before I even knew the disease existed. I am actively learning more about endometriosis and sharing my story because it is often overlooked even though it affects such a wide population of menstruating individuals. One in ten women worldwide is a significant number and more attention needs to be brought to the disease to mitigate years of living with symptoms and improve quality of life for menstruating individuals around the world.
Dr. Metz and Dr. Gregersen
Dr Christine N. Metz is head of the laboratory of medicinal biochemistry and a professor in the Center of Molecular Medicine at the Feinstein Institutes for Medical Research.
Dr. Gregersen has been working in the area of genetics for over two decades and led several major international consortia to study the genetics of rheumatoid arthritis, systemic lupus, myasthenia gravis, myositis, and other autoimmune disorders.
Dr. Metz and Dr. Gregersen
They told us that IGFBP-1 was a reliable biomarker for diagnosis of endometriosis. They elaborated that they were unsure of our use of PGE2 and PRL as biomarkers since hormones could be more difficult to isolate and detect. In conjunction with our modeling team, we determined that IGFBP-1 is accurate enough to be included in our diagnostic panel due to its high specificity and sensitivity, Despite concerns over the lengthy amount of time required to isolate this biomarker from patient samples. We further determined that we should exclude PGE2 and PRL for the aforementioned reasons as well as their limited effects on sensitivity and specificity.
Dr. Idhaliz Flores
Dr Flores is a professor of Basic Sciences, and OB-GYN at the Ponce Health Sciences University (PHSU) in Ponce, Puerto Rico. Since 2001, she has directed the Endometriosis Research Program (ERP) of the Ponce Research Institute. Her research interests include discovery of molecular biomarkers, inflammatory, and genetic/epigenetic factors of endometriosis and infertility.
Dr. Idhaliz Flores
Dr. Flores gave us a detailed presentation regarding the current directions of endometriosis research and the most promising pathways and biomarkers implicated in the disease. We had about 6 biomarkers in mind, and she confirmed the strength of our top biomarkers (IL-6, IL-1β, TNF-𝜶, IGFBP-1) for accurate diagnosis except PGE2, including several interleukins, which are all molecules associated with the chronic pain and inflammation experienced by patients. Additionally, to limit the use of equipment and complications of using too many biomarkers, Dr. Flores recommended we keep our diagnostic panel under 12 biomarkers and focus on pathways that have been identified numerous times in recent literature. This allows for an accurate test with a combination of unique biomarkers that can be carried out easily and efficiently. After this meeting, the team confirmed the use of IL-6, IL-1β, TNF-𝜶, and IGFBP-1 as biomarkers in our diagnostic panel.
Danielle is the Executive Director of Menstrual Health Hub (MH Hub), an female health non-profit organization that helps connect groups with female health experts and advocates. We originally met with her to help us connect with more endometriosis professionals. She said “you have to understand menstruation to understand endometriosis.” meaning that we need to educate the public about how menstruation works in order to make it clear to them how endometriosis works. So our team took the time to design a portion of our educational materials educating the public about the science and biology of women’s reproductive health, myths about endometriosis, as well as other women's reproductive diseases in our educational material.
Dr. Nicholas Hammond
Dr. Hammond is the assistant director of the workshop program provided by Center for Excellence in Teaching and Learning (CETL) at the University of Rochester, has expertise in Universal Design for Learning (UDL).
Dr. Nicholas Hammond
Talking to Dr. Hammond gave us clear guidelines and directions on how to effectively design our Upward Bound program for synthetic biology. He taught us how to design the course using backward design, where lessons are developed by first identifying learning objectives. Dr. Hammond also demonstrated how to design these objectives, with emphasis on making them small, measurable, and achievable. Implementing backward design, where lessons are developed by first identifying learning objectives, made our lessons more organized and clearer to the learner. Dr. Hammond also taught us the designing process of an interactive, virtual course. After we told him that we were planning to present the course using Powerpoint slides, he suggested that we add interactive questions during the lectures and hands-on activities, videos, and analogies to make the class more engaging and immersive. Based on this advice, we added interactive questions in our lectures, incorporated pictures and videos, and created activities for each lesson. He also advised us to create a syllabus and ask students to read relevant materials prior to the module so in the lesson we do not need to cover material that students could easily learn from reading. As a result, we added 10 minutes of relevant reading material prior to every module. We also incorporated his advice on developing an awarding system for students who complete the entire module, which includes a certificate and a letter written by our advisor, Dr. Anne S. Meyer.
Dr. Benjamin Miller and Jeffrey Beard
The Miller lab is one of the University of Rochester Medical Center labs. Dr. Miller is the principal investigator and Mr. Beard is a Ph.D. candidate who is currently working on cost-effective, robust, and user-friendly imaging methods. One of their main focuses is observing biomolecular interactions through developing new optical sensing technologies.
Dr. Benjamin Miller and Jeffrey Beard
During our first meeting, Dr. Miller and Mr. Benjamin gave us advice on possible experimental procedures for our lateral flow assay model; they also helped with giving some directions for simple and cost-effective imaging methods. Once we built our imaging station we met once again with the Miller lab to ask for their professional opinion on the product. They both expressed strong interest in our Lego-based design and they further gave us suggestions on how to further improve on it such as improving the accuracy of the light intensity and suggesting the use of ImageJ
Endometriosis Foundation of America：
Endometriosis Foundation of America
Endometriosis Foundation of America (Endofound) is a non-profit organization that aims to increase awareness of, provide advocacy, facilitate medical training, and fund endometriosis research. First, they emphasized the importance of improving the education about endometriosis and suggested that we should include the following facts about endometriosis in our brochure: “there is no diagnostic, other than management; ultimate treatment is excision; unfortunately it has recurrence” and “endometriosis is one of the leading causes of infertility”. Second, from their Endometriosis: Promoting Outreach and Wide Recognition (ENPOWR) project, we learned that the education of endometriosis should focus on both males and females. By educating both genders, girls are able to learn more about their own body and endometriosis and males are able to learn and apply the knowledge to the females surrounding them: mother, daughter, sister, wife, etc. Third, Endofound has two staff members, who are endometriosis patients, that have agreed to review our material. After the material was revised, they helped us distribute our materials including brochures and infographics. They also reached out to different universities to help us distribute our brochures on other campuses to increase awareness of endometriosis for a broader college student audience. Finally, regarding their LGBTQIA+ Project, we learned that there is limited research on endometriosis for LGBTQIA+, and most information is from non-scientific news articles which sometimes can be unreliable. Through the meeting with Endofound, we received useful suggestions to improve our material.
Early theories surrounding the presence and pathophysiology of endometriosis stated that it was a disease exclusively white women experienced (Bougie et al., 2019). Supporting this, by the 1950s literature reviews on endometriosis declared that there was an obvious connection between the presence of the disease and white wealthy women (Bougie et al., 2019). While outrageously false that endometriosis only affects wealthy white women, the claim has added to the racial bias colored women experience in healthcare (Hall et al., 2013). Yet, limited research to date has been achieved to aid in understanding how historical and current prejudice has influenced the research about the disease. Furthermore, the first review that characterizes endometriosis for transmasculine individuals has only emerged in research within the last year (2020) (Shim et al., 2020). The socioeconomic status of endometriosis patients and the implicit and systemic biases in healthcare have only added to the misdiagnosis under-diagnosis of the disease (Shim et al., 2020).
Social and Economic Challenge
Initially, to address the challenge of making our design accessible regardless of economic status or immediate healthcare access our team wanted to create an at-home diagnostic test (Yager et al., 2008, Bougie et al., 2019). However, when we mentioned this to Dr. Gubbels, she recommended that an in-clinic diagnostic may be more useful, as it could influence physicians to become more knowledgeable on endometriosis and help women receive diagnostics more quickly (Dr Ashley Gubbels, Personal Interview, May 2020). At the same time, the lack of established biomarkers with sufficient sensitivity and specificity prevented the design of a completely at-home test. For example, modeling shows the accuracy of our biomarker panel increases with the inclusion of one particular biomarker, IGFBP-1, yet the detection of IGFBP-1 requires additional laboratory skills and technique training for accuracy and safety (Nayyar et al., 2020). [link to wetlab] Additionally, the risks of non-precise sample treatments and the insufficient amount of sample increases the likelihood of inaccurate results (Koczula et al., 2016). We concluded the challenge of developing an accurate and safe at-home diagnostic panel is not a feasible goal and decided to develop into a clinical panel but did include an at-home component. There is still more discussion needed for in-clinic diagnosis as Dr. Holicov, the primary OB-GYN at Femina Clinic, in Romania, said “The lack of a specific biomarker significantly contributes to the delay of the diagnosis. However, both Dr. Stockman, a physician at the University of Rochester Medical Center, and Dr. Jones, the director of the Hudson Headwaters Health Network (a nonprofit system serving a medically underserved region), think that no matter if an effective treatment is available, a pre-screening test could provide concrete evidence of biological concerns that can help aid mental wellness and coping with pain (Dr. Stockman, Dr. Jones, Personal Interview, August 2020). Furthermore, we considered the ethics of having the diagnosis in medically underserved areas. As we talked with Dr. Stockman and Dr. Jones, we learned that it would not be a major obstacle to overcome since there are many healthcare networks, such as the Hudson Headwaters Health Network, that primarily work with the underserved areas and would provide the diagnosis and treatment service regardless if the patients can pay for it.